Is APBA2 p.Ser238Arg (c.712A>C) pathogenic?

APBA2 p.Ser238Arg (c.712A>C) is classified Uncertain significance in APBA2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-20). AlphaMissense: likely pathogenic (0.7292); Very rare (popmax 8.47e-05%, nfe).

How common is APBA2 p.Ser238Arg (c.712A>C) in the general population?

APBA2 p.Ser238Arg (c.712A>C) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about APBA2 p.Ser238Arg (c.712A>C)?

AlphaMissense predicts likely pathogenic (score 0.7292) — an in-silico prediction, not a clinical call.

APBA2 p.Ser238Arg

c.712A>C · VCV3878175

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7292 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.7292	likely pathogenic
REVEL	0.255	benign-leaning
SaProt	LLR -8.11	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 11	GERP 1.5, phastCons 1
Overall
CADD	23.5	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

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,180,022 alleles

Overall 6.2e-05% 1/1,614,130 alleles · very rare exomes 1/1,461,824 · genomes 0/152,306 · joint denominator

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.Ser238Arg
Coding: c.712A>C
MANE Select: NM_001353788
Type: single nucleotide variant
Location: chr15:29054596 (GRCh38)
Gene constraint: LOEUF 0.524 · pLI 0.78 (gnomAD)
Structure: AlphaFold pLDDT 59.74
Residue 238: the 'stxbp1-binding' region; the 'disordered' 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-ser238arg (accessed [today's date]).

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