Is ABCA4 p.Val615Ala (c.1844T>C) pathogenic?

ABCA4 p.Val615Ala (c.1844T>C) is classified Conflicting classifications of pathogenicity in ABCA4 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2023-06-23). AlphaMissense: ambiguous (0.3418); Absent from gnomAD v4.1; Associated with ABCA4-related disorder.

What condition is associated with ABCA4 p.Val615Ala (c.1844T>C)?

ABCA4 p.Val615Ala (c.1844T>C) is associated with ABCA4-related disorder (ClinVar).

How common is ABCA4 p.Val615Ala (c.1844T>C) in the general population?

ABCA4 p.Val615Ala (c.1844T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ABCA4 p.Val615Ala (c.1844T>C)?

AlphaMissense predicts ambiguous (score 0.3418) — an in-silico prediction, not a clinical call.

ABCA4 p.Val615Ala

c.1844T>C · rs2101078285 · VCV1066343

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

ambiguous

0.3418 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

ABCA4-related disorder

Computational evidence

Protein change
AlphaMissense	0.3418	ambiguous
REVEL	0.785	moderately pathogenic-leaning
SaProt	LLR -12.47	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.4	GERP 2, phastCons 0.99
Regional constraint	o/e 0.98	unconstrained · MANE · 128 kb · p 0.24 · regional, not allelic
Overall
CADD	22.8	PHRED · no single calibrated threshold — expert panels disagree

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.Val615Ala
Coding: c.1844T>C
MANE Select: NM_000350
dbSNP: rs2101078285
Type: single nucleotide variant
Location: chr1:94062670 (GRCh38)
Gene constraint: LOEUF 0.786 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.96 · 8 PDB
Residue 615: 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); an α-helix

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

Disease context

ABCA4-related disorder — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ABCA4 p.Val615Leu Uncertain significance ★ ⚠ same residue
ABCA4 p.Val615Phe Uncertain significance ★ ⚠ same residue
ABCA4 c.1099+2T>G Pathogenic/Likely pathogenic ★★ same condition
ABCA4 c.160+5G>C Pathogenic/Likely pathogenic ★★ same condition
ABCA4 c.1937+1G>C Pathogenic/Likely pathogenic ★★ same condition
ABCA4 c.1938-619A>G Pathogenic/Likely pathogenic ★★ same condition
ABCA4 c.2160+1G>C Pathogenic ★★ same condition
ABCA4 c.2161-8G>A 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-val615ala (accessed [today's date]).

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