Is AP2A2 p.Asn910His (c.2728A>C) pathogenic?

AP2A2 p.Asn910His (c.2728A>C) is classified Uncertain significance in AP2A2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-05). AlphaMissense: likely pathogenic (0.8363); Absent from gnomAD v4.1.

How common is AP2A2 p.Asn910His (c.2728A>C) in the general population?

AP2A2 p.Asn910His (c.2728A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about AP2A2 p.Asn910His (c.2728A>C)?

AlphaMissense predicts likely pathogenic (score 0.8363) — an in-silico prediction, not a clinical call.

AP2A2 p.Asn910His

c.2728A>C · VCV4641459

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8363 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.8363	likely pathogenic
REVEL	0.501	indeterminate
SaProt	LLR -7.71	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.8, phastCons 1
Regional constraint	o/e 0.72	unconstrained · MANE · 10 kb · p 5.7e-07 · regional, not allelic
Overall
CADD	27.1	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: AP2A2
Protein: p.Asn910His
Coding: c.2728A>C
MANE Select: NM_012305
Type: single nucleotide variant
Location: chr11:1009803 (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.Ala3Val Uncertain significance ★ ⚠ same type
AP2A2 p.Ala435Val 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-asn910his (accessed [today's date]).

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