Is ABCA4 p.Val256= (c.768G>A) pathogenic?

ABCA4 p.Val256= (c.768G>A) is classified Uncertain significance in ABCA4 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-12). Absent from gnomAD v4.1; Associated with severe early-childhood-onset retinal dystrophy.

What condition is associated with ABCA4 p.Val256= (c.768G>A)?

ABCA4 p.Val256= (c.768G>A) is associated with severe early-childhood-onset retinal dystrophy (ClinVar).

How common is ABCA4 p.Val256= (c.768G>A) in the general population?

ABCA4 p.Val256= (c.768G>A) is absent from gnomAD v4.1 (gnomAD).

How is Severe early-childhood-onset retinal dystrophy inherited?

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

ABCA4 p.Val256=

c.768G>A · VCV4292814

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

severe early-childhood-onset retinal dystrophy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.54	donor loss · deltas
Pangolin	Δ0.54	gain · loss 0.53 · SpliceAI calls loss · independent
Constraint at this position
Conservation	phyloP 7.7	GERP 1.9, phastCons 1
Overall
CADD	21.5	PHRED · no single calibrated threshold — expert panels disagree

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.Val256=
Coding: c.768G>A
MANE Select: NM_000350
Type: single nucleotide variant
Location: chr1:94098794 (GRCh38)
Gene constraint: LOEUF 0.786 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.96 · 8 PDB
Residue 256: 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)

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

Disease context

severe early-childhood-onset retinal dystrophy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Severe early-childhood-onset retinal dystrophy (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood, Infancy

Similar variants

ABCA4 p.Val256Leu Uncertain significance ★★ ⚠ same residue
ABCA4 c.1937+1G>A Pathogenic ★★★ same condition
ABCA4 c.3523-1G>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>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-val256 (accessed [today's date]).

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