Is ATP8A2 p.Ala761Val (c.2282C>T) pathogenic?

ATP8A2 p.Ala761Val (c.2282C>T) is classified Uncertain significance in ATP8A2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-12-19). AlphaMissense: likely pathogenic (0.6896); Ultra-rare (popmax 0.0103%, nfe); Associated with Inborn genetic diseases.

What condition is associated with ATP8A2 p.Ala761Val (c.2282C>T)?

ATP8A2 p.Ala761Val (c.2282C>T) is associated with Inborn genetic diseases (ClinVar).

How common is ATP8A2 p.Ala761Val (c.2282C>T) in the general population?

ATP8A2 p.Ala761Val (c.2282C>T) is ultra-rare (popmax 0.0103%, nfe) (gnomAD).

What do computational predictors say about ATP8A2 p.Ala761Val (c.2282C>T)?

AlphaMissense predicts likely pathogenic (score 0.6896) — an in-silico prediction, not a clinical call.

ATP8A2 p.Ala761Val

c.2282C>T · rs763604659 · VCV1501262

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.6896 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0103%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.6896	likely pathogenic
REVEL	0.67	pathogenic-leaning
SaProt	LLR -10.03	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 7.6	GERP 1.9, phastCons 1
Regional constraint	o/e 0.75	unconstrained · MANE · 288 kb · p 5e-12 · regional, not allelic
Overall
CADD	25.5	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

Grpmax group 0.0103% European (non-Finnish) · 121/1,179,688 alleles

Filtering AF 0.00876% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0082%

Overall 0.00818% 132/1,613,430 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0103%	9,750
Remaining individualsnot grpmax-eligible	0.0096%	10,413
African / African-American	0.004%	24,970
Admixed American	0.00334%	29,973

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: ATP8A2
Protein: p.Ala761Val
Coding: c.2282C>T
MANE Select: NM_016529
dbSNP: rs763604659
Type: single nucleotide variant
Location: chr13:25699243 (GRCh38)
Gene constraint: LOEUF 0.728 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 81.12
Residue 761: a UniProt-annotated variant site (in camrq4; uncertain significance)

Full ATP8A2 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

ATP8A2 p.Ala761= Likely benign ★ same residue
ATP8A2 p.Ala335Thr Uncertain significance ★★ ⚠ same condition
ATP8A2 p.Ala692Ser Uncertain significance ★★ ⚠ same condition
ATP8A2 p.Ala853Thr Uncertain significance ★★ ⚠ same condition
ATP8A2 p.Arg1120Trp Uncertain significance ★★ ⚠ same condition
ATP8A2 p.Arg1147Trp Uncertain significance ★★ ⚠ same condition
ATP8A2 p.Asn61Lys Uncertain significance ★★ ⚠ same condition
ATP8A2 p.Asp474Tyr 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/atp8a2-p-ala761val (accessed [today's date]).

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