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.4354G>T (p.Glu1452Ter)

CA10602429

236114 (ClinVar)

Gene: ABCA4 (HGNC:24)

Condition: ABCA4-related retinopathy (MONDO:0800406)

Inheritance Mode: Autosomal recessive inheritance

UUID: c7c4859f-11f7-434c-9ea3-58fb107410f9

Approved on: 2026-04-28

Published on: 2026-04-30

HGVS expressions

NM_000350.3:c.4354G>T

NM_000350.3(ABCA4):c.4354G>T (p.Glu1452Ter)

NC_000001.11:g.94029630C>A

CM000663.2:g.94029630C>A

NC_000001.10:g.94495186C>A

CM000663.1:g.94495186C>A

NC_000001.9:g.94267774C>A

NG_009073.1:g.96520G>T

ENST00000370225.4:c.4354G>T

ENST00000370225.3:c.4354G>T

ENST00000536513.5:c.730G>T

NM_000350.2:c.4354G>T

Pathogenic

PM3_Supporting PM2_Supporting PVS1

PS4

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.4354G>T; p.Glu1452Ter variant in ABCA4 is a nonsense variant predicted to cause a premature stop codon in biologically relevant exon 30 of 50 leading to nonsense mediated decay in a gene in which loss-of-function is an established disease mechanism (PVS1). This variant is absent from gnomAD v4.1.0 (PM2_Supporting). This variant has been detected in at least one individual with ABCA4-related retinopathy who was compound heterozygous for the variant and a pathogenic variant with phase unconfirmed (PM3_Supporting, PMID: 37705246). In summary, this variant meets the criteria to be classified as pathogenic for ABCA4-related retinopathy based on the ACMG/AMP criteria applied, as specified by the ClinGen ABCA4 VCEP (Specification Version 1.0.0): PVS1, PM3_Supporting, PM2_Supporting.

PM3_Supporting

This variant has been detected in at least one individual with ABCA4-related retinopathy was compound heterozygous for the variant and a pathogenic variant with phase unconfirmed (PM3 = 0.5 pts, PM3_Supporting, PMID: 37705246)

PM2_Supporting

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

PVS1

This is a nonsense variant located in exon 30 out of 50, and introduces a premature stop codon between codons 1-2255 (PVS1).

PS4

This variant is not in the Cornelis et al paper. (PMID: 35120629).

Curation History

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