ABCA4 p.Ala1791fs
c.5371dup · rs2523668736 · VCV2585325
ClinGen expert panel — ABCA4 VCEP
Pathogenic for ABCA4-related retinopathy. Applied ACMG criteria (verbatim):
PVS1 PM3_Supporting PM2_Supporting
Curation rationale (ClinGen, verbatim)
The NM_000350.3:c.5371dup (p.Ala1791GlyfsTer9) variant in ABCA4 is a frameshift variant predicted to cause a premature stop codon in biologically-relevant exon 38/50 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. This individual was compound heterozygous for the variant and a pathogenic variant (c.5882G>A; p.Gly1961Glu) presumed to be in trans by NGS targeted gene panel testing (PM3_Supporting; PMID: 31816670). 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): PVS1, PM3_Supporting, PM2_Supporting.
ClinGen Evidence Repository → · reported verbatim, not re-tallied by Sugi Variant.
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Consequence | frameshift | predicted loss-of-function |
|---|---|---|
| NMD | predicted | premature termination codon in exon 38 of 50 |
| Splicing | ||
| SpliceAI | — | not assessed · substitutions only |
| Constraint at this position | ||
| Conservation | phyloP 12 | GERP 1.7, phastCons 1 |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Population frequency
No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.
Variant & gene context
- Gene
- ABCA4
- Protein
- p.Ala1791fs
- Coding
- c.5371dup
- MANE Select
- NM_000350
- dbSNP
- rs2523668736
- Type
- Duplication
- Location
- chr1:94014631 (GRCh38)
- Gene constraint
- LOEUF 0.786 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 75.96 · 8 PDB
- Residue 1791
- a UniProt-annotated variant site (in cord3; uncertain significance); a UniProt-annotated variant site (in stgd1; uncertain significance); a UniProt-annotated variant site (found in a patient with chorioretinal atrophy; uncertain significance); a UniProt-annotated variant site (found in a patient with macular dystrophy; uncertain significance); a UniProt-annotated variant site (in stgd1 and cord3; uncertain significance); a UniProt-annotated variant site (sequence variant); a UniProt-annotated variant site (in stgd1 and ffm; uncertain significance); an α-helix
Similar variants
- ABCA4 p.Ser1071fs Pathogenic ★★★ same condition
- ABCA4 c.858+4dup Uncertain significance ★★★ same condition
- ABCA4 p.Asn99fs Pathogenic ★★ same condition
- ABCA4 p.Gly1110fs Pathogenic/Likely pathogenic ★★ same condition
- ABCA4 p.Ser84fs Pathogenic/Likely pathogenic ★★ same condition
- ABCA4 p.Val2236fs Pathogenic/Likely pathogenic ★★ same condition
- ABCA4 c.1356+4dup Conflicting classifications of pathogenicity ★ same condition
- ABCA4 p.Ala1791Val Uncertain significance ★ same residue
Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →
Cite Sugi Variant
Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/abca4-p-ala1791fs (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown