Is BCAP31 p.Gln125Arg (c.374A>G) pathogenic?

BCAP31 p.Gln125Arg (c.374A>G) is classified Uncertain significance in BCAP31 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-18). AlphaMissense: likely benign (0.1747); Very rare (popmax 0.00349%, afr).

How common is BCAP31 p.Gln125Arg (c.374A>G) in the general population?

BCAP31 p.Gln125Arg (c.374A>G) is very rare (popmax 0.00349%, afr) (gnomAD).

What do computational predictors say about BCAP31 p.Gln125Arg (c.374A>G)?

AlphaMissense predicts likely benign (score 0.1747) — an in-silico prediction, not a clinical call.

BCAP31 p.Gln125Arg

c.374A>G · rs1314585732 · VCV1937288

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1747 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00349%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1747	likely benign
REVEL	0.166	moderately benign-leaning
SaProt	LLR -9.34	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.39	acceptor loss · deltas
Constraint at this position
Conservation	phyloP 7.8	GERP 1.7, phastCons 1
Regional constraint	o/e 0.64	unconstrained · MANE · 22 kb · p 6.9e-07 · regional, not allelic
Overall
CADD	25.2	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 0.00349% African / African-American · 2/57,359 alleles

Filtering AF 0.000578% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000216%

Overall 0.000165% 2/1,209,642 alleles · very rare

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: BCAP31
Protein: p.Gln125Arg
Coding: c.374A>G
MANE Select: NM_001256447
dbSNP: rs1314585732
Type: single nucleotide variant
Location: chrX:153704062 (GRCh38)
Structure: AlphaFold pLDDT 84.74 · 3 PDB

Full BCAP31 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

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BCAP31 p.Gly239Asp Uncertain significance ★★ ⚠ same type
BCAP31 p.Ile56Val Uncertain significance ★★ ⚠ same type
BCAP31 p.Leu226Val Uncertain significance ★★ ⚠ same type
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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/bcap31-p-gln125arg (accessed [today's date]).

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