Is APBA2 p.Arg211Cys (c.631C>T) pathogenic?

APBA2 p.Arg211Cys (c.631C>T) is classified Uncertain significance in APBA2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-07-26). AlphaMissense: likely benign (0.0645); Ultra-rare (popmax 0.0468%, amr).

How common is APBA2 p.Arg211Cys (c.631C>T) in the general population?

APBA2 p.Arg211Cys (c.631C>T) is ultra-rare (popmax 0.0468%, amr) (gnomAD).

What do computational predictors say about APBA2 p.Arg211Cys (c.631C>T)?

AlphaMissense predicts likely benign (score 0.0645) — an in-silico prediction, not a clinical call.

APBA2 p.Arg211Cys

c.631C>T · rs149847107 · VCV2253945

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0645 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0468%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0645	likely benign
REVEL	0.079	moderately benign-leaning
SaProt	LLR -7.00	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 0.36	GERP -0.95
Overall
CADD	18.74	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 0.0468% Admixed American · 28/59,870 alleles

Filtering AF 0.0332% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0287%

Overall 0.00502% 81/1,613,394 alleles · ultra-rare exomes 62/1,461,074 · genomes 19/152,320 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0468%	2,138
African / African-American	0.02%	5,004
Middle Eastern	0.0165%	6,062
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,552
Finnishnot grpmax-eligible	0.00313%	31,987
European (non-Finnish)	0.00271%	36,866
South Asian	0.0022%	45,478

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.Arg211Cys
Coding: c.631C>T
MANE Select: NM_001353788
dbSNP: rs149847107
Type: single nucleotide variant
Location: chr15:29054515 (GRCh38)
Gene constraint: LOEUF 0.524 · pLI 0.78 (gnomAD)
Structure: AlphaFold pLDDT 59.74
Residue 211: the 'disordered' region; the 'stxbp1-binding' region

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-arg211cys (accessed [today's date]).

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