Is APBA2 p.Ala417Val (c.1250C>T) pathogenic?

APBA2 p.Ala417Val (c.1250C>T) is classified Uncertain significance in APBA2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-15). AlphaMissense: likely benign (0.1607); Ultra-rare (popmax 0.045%, amr).

How common is APBA2 p.Ala417Val (c.1250C>T) in the general population?

APBA2 p.Ala417Val (c.1250C>T) is ultra-rare (popmax 0.045%, amr) (gnomAD).

What do computational predictors say about APBA2 p.Ala417Val (c.1250C>T)?

AlphaMissense predicts likely benign (score 0.1607) — an in-silico prediction, not a clinical call.

APBA2 p.Ala417Val

c.1250C>T · rs766376050 · VCV3127635

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1607 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.045%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1607	likely benign
REVEL	0.052	moderately benign-leaning
SaProt	LLR -6.15	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.53 · evaluated, not missing
Pangolin	Δ0.21	loss · gain 0.01 · SpliceAI below 0.2 · independent
Constraint at this position
Conservation	phyloP 2.1	GERP 1.5, phastCons 1
Overall
CADD	27.0	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 0.045% Admixed American · 27/60,018 alleles

Filtering AF 0.0317% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0273%

Overall 0.00297% 48/1,614,038 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.045%	2,223
Middle Eastern	0.0164%	6,084
Remaining individualsnot grpmax-eligible	0.016%	6,248
African / African-American	0.004%	24,979
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,604
South Asian	0.00329%	30,363
European (non-Finnish)	0.000254%	393,329

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.Ala417Val
Coding: c.1250C>T
MANE Select: NM_001353788
dbSNP: rs766376050
Type: single nucleotide variant
Location: chr15:29094312 (GRCh38)
Gene constraint: LOEUF 0.524 · pLI 0.78 (gnomAD)
Structure: AlphaFold pLDDT 59.74
Residue 417: the pid domain

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

Similar variants

APBA2 p.Val77Met Uncertain significance ★★ ⚠ same type
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

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-ala417val (accessed [today's date]).

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