Is ABCA4 p.Asp613Val (c.1838A>T) pathogenic?

ABCA4 p.Asp613Val (c.1838A>T) is classified Uncertain significance in ABCA4 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-01-27). AlphaMissense: likely pathogenic (0.9267); Absent from gnomAD v4.1; Associated with cone dystrophy.

What condition is associated with ABCA4 p.Asp613Val (c.1838A>T)?

ABCA4 p.Asp613Val (c.1838A>T) is associated with cone dystrophy (ClinVar).

How common is ABCA4 p.Asp613Val (c.1838A>T) in the general population?

ABCA4 p.Asp613Val (c.1838A>T) is absent from gnomAD v4.1 (gnomAD).

How is Progressive cone dystrophy inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about ABCA4 p.Asp613Val (c.1838A>T)?

AlphaMissense predicts likely pathogenic (score 0.9267) — an in-silico prediction, not a clinical call.

ABCA4 p.Asp613Val

c.1838A>T · rs2101078303 · VCV1382097

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9267 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

cone dystrophy

Computational evidence

Protein change
AlphaMissense	0.9267	likely pathogenic · top 7% in ABCA4
REVEL	0.942	strongly pathogenic-leaning
SaProt	LLR -8.33	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 2, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 128 kb · p 0.24 · regional, not allelic
Overall
CADD	28.4	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.Asp613Val
Coding: c.1838A>T
MANE Select: NM_000350
dbSNP: rs2101078303
Type: single nucleotide variant
Location: chr1:94062676 (GRCh38)
Gene constraint: LOEUF 0.786 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.96 · 8 PDB
Residue 613: 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

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

For Progressive cone dystrophy (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive
Onset: Adult

Similar variants

ABCA4 p.Asp613Gly Uncertain significance ★ ⚠ same residue
ABCA4 p.Gln2220Ter Pathogenic ★★★ same condition
ABCA4 p.Gly1961Glu Pathogenic ★★★ same condition
ABCA4 p.Val2050Leu Likely benign ★★★ ⚠ same condition
ABCA4 c.6005+1G>A Pathogenic ★★ same condition
ABCA4 p.Trp1724Ter Pathogenic/Likely pathogenic ★★ same condition
ABCA4 p.Gly1065Asp Conflicting classifications of pathogenicity ★ ⚠ same condition
ABCA4 p.Gly1591Arg Conflicting classifications of pathogenicity ★ ⚠ 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-asp613val (accessed [today's date]).

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