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.5753A>G (p.Asp1918Gly)

CA341280424

1481126 (ClinVar)

Gene: ABCA4 (HGNC:24)

Condition: ABCA4-related retinopathy (MONDO:0800406)

Inheritance Mode: Autosomal recessive inheritance

UUID: b2e8e9b3-bc76-402c-9403-7ada994befae

Approved on: 2026-05-26

Published on: 2026-05-26

HGVS expressions

NM_000350.3(ABCA4):c.5753A>G (p.Asp1918Gly)

NM_000350.3:c.5753A>G

NC_000001.11:g.94008833T>C

CM000663.2:g.94008833T>C

NC_000001.10:g.94474389T>C

CM000663.1:g.94474389T>C

NC_000001.9:g.94246977T>C

NG_009073.1:g.117317A>G

ENST00000370225.4:c.5753A>G

ENST00000370225.3:c.5753A>G

ENST00000465352.1:n.169A>G

ENST00000536513.5:c.2129A>G

NM_000350.2:c.5753A>G

Likely Pathogenic

PM3_Supporting PP3_Moderate PM5 PM2_Supporting

PP4 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.5753A>G variant in ABCA4 is a missense variant predicted to cause substitution of aspartic acid by glycine at amino acid 1918; p.Asp1918Gly. This variant is absent from gnomAD v4.1.0 meeting PM2_Supporting. The computational predictor REVEL gives a score of 0.836 which is above the threshold of >0.772 meeting PP3_Moderate. This variant has been detected in one individual with ABCA4-related retinopathy who is compound heterozygous for the variant and a pathogenic variant suspected in trans (PM3_Supporting; PMID: 26492201). Another missense variant, c.5753A>T; p.Asp1918Val (ClinVar Variation ID: 871507), in the same codon has been classified as pathogenic for ABCA4-related retinopathy by the ClinGen ABCA4 VCEP, and Splice AI revealed no expected effects on splicing (PM5). 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 v.1.0.0): PM3_Supporting, PP3_Moderate, PM5, PM2_Supporting.

PM3_Supporting

This variant has been detected in one individual with ABCA4-related retinopathy who is compound heterozygous for the variant and a pathogenic variant that is suspected to be in trans (PMID: 26492201, PM3_Supporting).

PP3_Moderate

The computational predictor REVEL gives a score of 0.836 which is above the threshold of >0.772, evidence that predicts a damaging effect on ABCA4 function (PP3_Moderate).

PM5

Another missense variant, c.5753A>T, p.Asp1918Val (PMID: 27939946, ClinVar Variation ID 871507), in the same codon has been classified as pathogenic for ABCA4-related retinopathy by the ClinGen ABCA4 VCEP, and Splice AI (score = 0.1) revealed no expected effects on splicing (PM5_Moderate).

PM2_Supporting

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

PP4

PMID: 26492201. Subject 18: Male, onset at 15 years of age, BCVA of 0.82, Full Field Flash electroretinogram normal result (only the macula is affected). Microarray chip detected compound het c.5882G>A and c.5753A>G in ABCA4. Macular flecks on imaging and/or fundus autofluorescence and/or beaten-bronze appearance not specified for this patient. PP4_Not met

PS4

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

Curation History

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