Evidence Repository - Clinical Genome Resources

The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]

Variant: NM_002880.4(RAF1):c.935T>C (p.Val312Ala)

Curation Version - 2.0
Curation History
JSON LD for Version 2.0

CA177679

40612 (ClinVar)

Gene: RAF1

Condition: RASopathy

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 5dd4045c-aa85-4341-8238-7a7b67f85d3f

Approved on: 2024-12-03

Published on: 2025-03-25

HGVS expressions

NM_002880.4:c.935T>C

NM_002880.4(RAF1):c.935T>C (p.Val312Ala)

NC_000003.12:g.12600207A>G

CM000665.2:g.12600207A>G

NC_000003.11:g.12641706A>G

CM000665.1:g.12641706A>G

NC_000003.10:g.12616706A>G

NG_007467.1:g.68973T>C

ENST00000423275.6:c.*600T>C

ENST00000432427.3:c.255T>C

ENST00000465826.6:n.526T>C

ENST00000491290.2:n.1312T>C

ENST00000684903.1:c.*612T>C

ENST00000685348.1:c.*612T>C

ENST00000685437.1:c.836T>C

ENST00000685438.1:n.699T>C

ENST00000685653.1:c.935T>C

ENST00000685738.1:c.935T>C

ENST00000686409.1:n.1643T>C

ENST00000686455.1:n.1298T>C

ENST00000686479.1:n.1306T>C

ENST00000686762.1:c.935T>C

ENST00000687257.1:n.1171T>C

ENST00000687326.1:c.935T>C

ENST00000687486.1:c.182+181T>C

ENST00000687505.1:n.1053T>C

ENST00000687923.1:c.836T>C

ENST00000687940.1:n.1312T>C

ENST00000688269.1:n.1531T>C

ENST00000688326.1:c.255T>C

ENST00000688444.1:n.1261T>C

ENST00000688543.1:c.836T>C

ENST00000688625.1:c.*513T>C

ENST00000688803.1:n.1166T>C

ENST00000689097.1:c.*612T>C

ENST00000689389.1:c.935T>C

ENST00000689418.1:c.*612T>C

ENST00000689481.1:c.*612T>C

ENST00000689540.1:n.1085T>C

ENST00000689876.1:c.935T>C

ENST00000689914.1:c.935T>C

ENST00000690397.1:c.824T>C

ENST00000690460.1:c.923T>C

ENST00000690625.1:n.1238T>C

ENST00000691268.1:c.362T>C

ENST00000691396.1:c.*728T>C

ENST00000691724.1:c.935T>C

ENST00000691779.1:c.*513T>C

ENST00000691899.1:c.935T>C

ENST00000692069.1:n.1158T>C

ENST00000692093.1:c.836T>C

ENST00000692311.1:n.1416T>C

ENST00000692558.1:n.1300T>C

ENST00000692773.1:c.*672T>C

ENST00000692830.1:c.*680T>C

ENST00000693069.1:c.836T>C

ENST00000693312.1:c.710T>C

ENST00000693664.1:c.935T>C

ENST00000693705.1:c.*612T>C

ENST00000251849.9:c.935T>C

ENST00000442415.7:c.995T>C

ENST00000251849.8:c.935T>C

ENST00000423275.5:c.*612T>C

ENST00000432427.2:c.572T>C

ENST00000442415.6:c.995T>C

ENST00000465826.5:n.179T>C

ENST00000491290.1:n.564T>C

NM_002880.3:c.935T>C

NM_001354689.1:c.995T>C

NM_001354690.1:c.935T>C

NM_001354691.1:c.692T>C

NM_001354692.1:c.692T>C

NM_001354693.1:c.836T>C

NM_001354694.1:c.752T>C

NM_001354695.1:c.593T>C

NR_148940.1:n.1350T>C

NR_148941.1:n.1350T>C

NR_148942.1:n.1350T>C

NM_001354689.3:c.995T>C

NM_001354690.2:c.935T>C

NM_001354691.2:c.692T>C

NM_001354692.2:c.692T>C

NM_001354693.2:c.836T>C

NM_001354694.2:c.752T>C

NM_001354695.2:c.593T>C

NR_148940.2:n.1266T>C

NR_148941.2:n.1266T>C

NR_148942.2:n.1266T>C

NM_001354690.3:c.935T>C

NM_001354691.3:c.692T>C

NM_001354692.3:c.692T>C

NM_001354693.3:c.836T>C

NM_001354694.3:c.752T>C

NM_001354695.3:c.593T>C

NR_148940.3:n.1266T>C

NR_148941.3:n.1266T>C

NR_148942.3:n.1266T>C

Likely Benign

BP5 BP4

Evidence Links 0

Expert Panel

RASopathy VCEP

Criteria Specification Information

Criteria Specification: ClinGen RASopathy Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for RAF1 Version 2.3.0

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

RASopathy VCEP

The c.935T>C (p.Val312Ala) variant in the RAF1 gene is a missense variant predicted to cause substitution of valine by alanine at amino acid 312. The computational predictor REVEL gives a score of 0.174, which is below the threshold of 0.3 and does not predict a damaging effect on RAF1 function (BP4). Additionally, this variant was identified in a case with an alternate molecular basis for disease (BP5; GeneDx, Partners LMM internal data; GTR ID's: 26957, 21766; ClinVar SCV000200036.4; SCV000209006.12). In summary, this variant meets criteria to be classified as likely benign for autosomal dominant RASopathies based on the ACMG/AMP criteria applied, as specified by the ClinGen RASopathy Variant Curation Expert Panel: BP4, BP5. (Specification Version 2.3, 12/3/2024)

BP5

Variant identified in a case with an alternate molecular basis for disease (GeneDx, Partners LMM internal data; GTR ID's: 26957, 21766; ClinVar SCV000200036.4; SCV000209006.12)

BP4

Computational prediction tools and conservation analysis suggest that the p.Val312Ala variant does not impact the protein (REVEL score of 0.174).

Curation History

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