Is APBA3 p.Asp2Val (c.5A>T) pathogenic?

APBA3 p.Asp2Val (c.5A>T) is classified Uncertain significance in APBA3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-12). AlphaMissense: likely benign (0.1524); Very rare (popmax 0.00269%, afr).

How common is APBA3 p.Asp2Val (c.5A>T) in the general population?

APBA3 p.Asp2Val (c.5A>T) is very rare (popmax 0.00269%, afr) (gnomAD).

What do computational predictors say about APBA3 p.Asp2Val (c.5A>T)?

AlphaMissense predicts likely benign (score 0.1524) — an in-silico prediction, not a clinical call.

APBA3 p.Asp2Val

c.5A>T · VCV3924577

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1524 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00269%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1524	likely benign
REVEL	0.041	moderately benign-leaning
SaProt	LLR -7.11	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 4.8	GERP 0.33, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 9,235 bp · p 0.12 · regional, not allelic
Overall
CADD	19.66	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 0.00269% African / African-American · 2/74,470 alleles

Filtering AF 0.00069% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00054%

Overall 0.00106% 17/1,597,400 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00269%	37,235
Remaining individualsnot grpmax-eligible	0.00161%	62,120
European (non-Finnish)	0.00119%	84,138

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: APBA3
Protein: p.Asp2Val
Coding: c.5A>T
MANE Select: NM_004886
Type: single nucleotide variant
Location: chr19:3760260 (GRCh38)
Gene constraint: LOEUF 1.237 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 64.79 · 3 PDB
Residue 2: the 'disordered' region

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-asp2val (accessed [today's date]).

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