Is APBA3 p.Ala432Val (c.1295C>T) pathogenic?

APBA3 p.Ala432Val (c.1295C>T) is classified Uncertain significance in APBA3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-05). AlphaMissense: likely pathogenic (0.8155); Absent from gnomAD v4.1.

How common is APBA3 p.Ala432Val (c.1295C>T) in the general population?

APBA3 p.Ala432Val (c.1295C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about APBA3 p.Ala432Val (c.1295C>T)?

AlphaMissense predicts likely pathogenic (score 0.8155) — an in-silico prediction, not a clinical call.

APBA3 p.Ala432Val

c.1295C>T · VCV3405216

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8155 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,586,158)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8155	likely pathogenic
REVEL	0.724	pathogenic-leaning
SaProt	LLR -9.67	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 11	GERP 2.1, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 9,235 bp · p 0.12 · regional, not allelic
Overall
CADD	23.9	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

No allele count reported in gnomAD v4.1 (AN 1,586,158). 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: APBA3
Protein: p.Ala432Val
Coding: c.1295C>T
MANE Select: NM_004886
Type: single nucleotide variant
Location: chr19:3752608 (GRCh38)
Gene constraint: LOEUF 1.237 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 64.79 · 3 PDB
Residue 432: the pdz 1 domain

Full APBA3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

APBA3 p.Ala158Val Uncertain significance ★ ⚠ same type
APBA3 p.Ala202Val Uncertain significance ★ ⚠ same type
APBA3 p.Ala223Val Uncertain significance ★ ⚠ same type
APBA3 p.Ala308Val Uncertain significance ★ ⚠ same type
APBA3 p.Ala317Val Uncertain significance ★ ⚠ same type
APBA3 p.Ala335Thr Uncertain significance ★ ⚠ same type
APBA3 p.Ala335Val Uncertain significance ★ ⚠ same type
APBA3 p.Ala351Thr 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/apba3-p-ala432val (accessed [today's date]).

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