Is ABCA4 p.Leu760Val (c.2278C>G) pathogenic?

ABCA4 p.Leu760Val (c.2278C>G) is classified Conflicting classifications of pathogenicity in ABCA4 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2026-02-17). AlphaMissense: likely benign (0.1326); Very rare (popmax 8.47e-05%, nfe); Associated with Inborn genetic diseases.

What condition is associated with ABCA4 p.Leu760Val (c.2278C>G)?

ABCA4 p.Leu760Val (c.2278C>G) is associated with Inborn genetic diseases (ClinVar).

How common is ABCA4 p.Leu760Val (c.2278C>G) in the general population?

ABCA4 p.Leu760Val (c.2278C>G) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about ABCA4 p.Leu760Val (c.2278C>G)?

AlphaMissense predicts likely benign (score 0.1326) — an in-silico prediction, not a clinical call.

ABCA4 p.Leu760Val

c.2278C>G · rs886046566 · VCV298257

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1326 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1326	likely benign
REVEL	0.293	indeterminate
SaProt	LLR -4.90	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.6	GERP 0.15, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 128 kb · p 0.24 · regional, not allelic
Overall
CADD	18.77	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

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,180,022 alleles

Overall 6.84e-05% 1/1,461,810 alleles · very rare

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: ABCA4
Protein: p.Leu760Val
Coding: c.2278C>G
MANE Select: NM_000350
dbSNP: rs886046566
Type: single nucleotide variant
Location: chr1:94056705 (GRCh38)
Gene constraint: LOEUF 0.786 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.96 · 8 PDB
Residue 760: 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); an α-helix; a disulfide bond

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ABCA4 p.Leu760Pro Likely pathogenic ★ ⚠ same residue
ABCA4 p.Ala1287Val Uncertain significance ★★ ⚠ same condition
ABCA4 p.Ala1324Val Uncertain significance ★★ ⚠ same condition
ABCA4 p.Ala45Gly Uncertain significance ★★ ⚠ same condition
ABCA4 p.Arg1170Thr Uncertain significance ★★ ⚠ same condition
ABCA4 p.Arg140Pro Uncertain significance ★★ ⚠ same condition
ABCA4 p.Arg1963His Uncertain significance ★★ ⚠ same condition
ABCA4 p.Arg487Pro Uncertain significance ★★ ⚠ 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-leu760val (accessed [today's date]).

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