Is ABCA4 p.Ala2037Val (c.6110C>T) pathogenic?

ABCA4 p.Ala2037Val (c.6110C>T) is classified Uncertain significance in ABCA4 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-10-01). AlphaMissense: likely pathogenic (0.6511); Absent from gnomAD v4.1; Associated with inherited retinal dystrophy.

What condition is associated with ABCA4 p.Ala2037Val (c.6110C>T)?

ABCA4 p.Ala2037Val (c.6110C>T) is associated with inherited retinal dystrophy (ClinVar).

How common is ABCA4 p.Ala2037Val (c.6110C>T) in the general population?

ABCA4 p.Ala2037Val (c.6110C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ABCA4 p.Ala2037Val (c.6110C>T)?

AlphaMissense predicts likely pathogenic (score 0.6511) — an in-silico prediction, not a clinical call.

ABCA4 p.Ala2037Val

c.6110C>T · rs1659353253 · VCV866865

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.6511 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

inherited retinal dystrophy

Computational evidence

Protein change
AlphaMissense	0.6511	likely pathogenic
REVEL	0.931	moderately pathogenic-leaning
SaProt	LLR -12.41	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 128 kb · p 0.24 · regional, not allelic
Overall
CADD	29.4	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ABCA4
Protein: p.Ala2037Val
Coding: c.6110C>T
MANE Select: NM_000350
dbSNP: rs1659353253
Type: single nucleotide variant
Location: chr1:94005478 (GRCh38)
Gene constraint: LOEUF 0.786 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.96 · 8 PDB
Residue 2037: 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); the abc transporter 2 domain; 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

Full ABCA4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

inherited retinal dystrophy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ABCA4 p.Ala2037Thr Conflicting classifications of pathogenicity ★ ⚠ same residue
ABCA4 c.1937+1G>A Pathogenic ★★★ same condition
ABCA4 c.4253+43G>A Pathogenic ★★★ same condition
ABCA4 c.4254-1G>C Pathogenic ★★★ same condition
ABCA4 c.4352+1G>A Pathogenic ★★★ same condition
ABCA4 c.4773+3A>G Pathogenic ★★★ same condition
ABCA4 c.5018+2T>A Pathogenic ★★★ same condition
ABCA4 c.5018+2T>C Pathogenic ★★★ same condition

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-ala2037val (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown