Is AP2A2 p.Ala3Val (c.8C>T) pathogenic?

AP2A2 p.Ala3Val (c.8C>T) is classified Uncertain significance in AP2A2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-31). AlphaMissense: likely benign (0.3363); Absent from gnomAD v4.1.

How common is AP2A2 p.Ala3Val (c.8C>T) in the general population?

AP2A2 p.Ala3Val (c.8C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about AP2A2 p.Ala3Val (c.8C>T)?

AlphaMissense predicts likely benign (score 0.3363) — an in-silico prediction, not a clinical call.

AP2A2 p.Ala3Val

c.8C>T · VCV4114954

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3363 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,411,210)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.3363	likely benign
REVEL	0.15	moderately benign-leaning
SaProt	LLR -7.01	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.9	GERP 1.4, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 33 kb · p 0.56 · regional, not allelic
Overall
CADD	23.4	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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

No allele count reported in gnomAD v4.1 (AN 1,411,210). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: AP2A2
Protein: p.Ala3Val
Coding: c.8C>T
MANE Select: NM_012305
Type: single nucleotide variant
Location: chr11:926029 (GRCh38)
Gene constraint: LOEUF 0.437 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 85.30

Full AP2A2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

AP2A2 p.Ala136Ser Uncertain significance ★ ⚠ same type
AP2A2 p.Ala136Thr Uncertain significance ★ ⚠ same type
AP2A2 p.Ala168Thr Uncertain significance ★ ⚠ same type
AP2A2 p.Ala274Pro Uncertain significance ★ ⚠ same type
AP2A2 p.Ala304Val Uncertain significance ★ ⚠ same type
AP2A2 p.Ala375Thr Uncertain significance ★ ⚠ same type
AP2A2 p.Ala435Val Uncertain significance ★ ⚠ same type
AP2A2 p.Ala488Thr Uncertain significance ★ ⚠ same type

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/ap2a2-p-ala3val (accessed [today's date]).

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