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_000350.3(ABCA4):c.6091G>A (p.Glu2031Lys)

CA341279017

866538 (ClinVar)

Gene: ABCA4 (HGNC:24)

Condition: ABCA4-related retinopathy (MONDO:0800406)

Inheritance Mode: Autosomal recessive inheritance

UUID: 181d201f-3a36-4c8b-b399-227e4a87a1b0

Approved on: 2026-05-05

Published on: 2026-05-17

HGVS expressions

NM_000350.3(ABCA4):c.6091G>A (p.Glu2031Lys)

NM_000350.3:c.6091G>A

NC_000001.11:g.94005497C>T

CM000663.2:g.94005497C>T

NC_000001.10:g.94471053C>T

CM000663.1:g.94471053C>T

NC_000001.9:g.94243641C>T

NG_009073.1:g.120653G>A

ENST00000370225.4:c.6091G>A

ENST00000370225.3:c.6091G>A

ENST00000465352.1:n.507G>A

ENST00000484388.1:n.205G>A

ENST00000536513.5:c.2467G>A

NM_000350.2:c.6091G>A

Likely Pathogenic

PM2_Supporting PP3_Moderate PM3_Strong

PS4 PP4

Evidence Links 0

Expert Panel

ABCA4 VCEP

Criteria Specification Information

Criteria Specification: ClinGen ABCA4 Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for ABCA4 Version 1.0.0

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

ABCA4 VCEP

The NM_000350.3(ABCA4):c.6091G>A variant in ABCA4 is a missense variant predicted to cause substitution of glutamic acid by lysine at amino acid 2031 (p.Glu2031Lys). This variant is absent from gnomAD v4.1.0 meeting PM2_Supporting. The computational predictor REVEL gives a score of 0.947 which is above the threshold of >0.772 meeting PP3_Moderate. This variant has been detected in at least 4 individuals with ABCA4-related retinopathy. These individuals were compound heterozygous for the variant and a known pathogenic variant, which was not confirmed in trans (PM3_Strong; PMID: 38309476, Clinical Diagnostic Lab). In summary, this variant meets the criteria to be classified as likely pathogenic for ABCA4-related retinopathy based on the ACMG/AMP criteria applied, as specified by the ClinGen ABCA4 VCEP specification version 1.0.0: PM3_Strong, PM2_Supporting, PP3_Moderate.

PM2_Supporting

This variant is absent from gnomAD v4.1.0 (PM2_Supporting).

PP3_Moderate

The computational predictor REVEL gives a score of 0.947 which is above the threshold of >0.772, evidence that predicts a damaging effect on ABCA4 function (PP3_Moderate).

PM3_Strong

This variant has been detected in at least 4 individuals with ABCA4-related retinopathy. These individuals were compound heterozygous for the variant and a known pathogenic variant, which was not confirmed in trans (PM3=2 points; PM3_Strong; PMID: 38309476, Clinical Diagnostic Lab).

PS4

This variant was not evaluated in the Cornelis et. al paper.

PP4

One individual with this variant was said to have ABCA4-associated retinal disease, but their phenotype was not specified so they do not meet the PP4 criteria established by the ABCA4 VCEP (PMID: 38309476).

Curation History

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