Is APBA2 p.Val77Met (c.229G>A) pathogenic?

APBA2 p.Val77Met (c.229G>A) is classified Uncertain significance in APBA2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-05-31). AlphaMissense: likely benign (0.285); Very rare (popmax 0.00133%, afr).

How common is APBA2 p.Val77Met (c.229G>A) in the general population?

APBA2 p.Val77Met (c.229G>A) is very rare (popmax 0.00133%, afr) (gnomAD).

What do computational predictors say about APBA2 p.Val77Met (c.229G>A)?

AlphaMissense predicts likely benign (score 0.285) — an in-silico prediction, not a clinical call.

APBA2 p.Val77Met

c.229G>A · rs140795962 · VCV1686445

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.285 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.285	likely benign
REVEL	0.222	benign-leaning
SaProt	LLR -7.03	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 8.5	GERP 1.5, phastCons 1
Overall
CADD	26.2	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

Grpmax group 0.00133% African / African-American · 1/74,930 alleles

Filtering AF 0.000688% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000539%

Overall 0.000929% 15/1,614,038 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00133%	74,930
European (non-Finnish)	0.00119%	84,289

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: APBA2
Protein: p.Val77Met
Coding: c.229G>A
MANE Select: NM_001353788
dbSNP: rs140795962
Type: single nucleotide variant
Location: chr15:29054113 (GRCh38)
Gene constraint: LOEUF 0.524 · pLI 0.78 (gnomAD)
Structure: AlphaFold pLDDT 59.74
Residue 77: the 'disordered' region

Full APBA2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

APBA2 c.1216-9T>C Benign ★★ same type
APBA2 c.1525-8C>G Likely benign ★★ same type
APBA2 c.1705-9C>T Benign ★★ same type
APBA2 p.Asp87= Benign ★★ same type
APBA2 p.Gly206= Benign ★★ same type
APBA2 p.His127= Benign ★★ same type
APBA2 p.Ile101= Benign ★★ same type
APBA2 p.Ile512= Benign ★★ 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/apba2-p-val77met (accessed [today's date]).

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