Is BCAP31 p.Arg118Cys (c.352C>T) pathogenic?

BCAP31 p.Arg118Cys (c.352C>T) is classified Uncertain significance in BCAP31 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-23). AlphaMissense: likely pathogenic (0.8252); Ultra-rare (popmax 0.0247%, mid).

How common is BCAP31 p.Arg118Cys (c.352C>T) in the general population?

BCAP31 p.Arg118Cys (c.352C>T) is ultra-rare (popmax 0.0247%, mid) (gnomAD).

What do computational predictors say about BCAP31 p.Arg118Cys (c.352C>T)?

AlphaMissense predicts likely pathogenic (score 0.8252) — an in-silico prediction, not a clinical call.

BCAP31 p.Arg118Cys

c.352C>T · rs1420709522 · VCV1303401

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.8252 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0247%, mid)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8252	likely pathogenic
REVEL	0.703	pathogenic-leaning
SaProt	LLR -14.41	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	Δ0.20	acceptor gain · deltas
Constraint at this position
Conservation	phyloP 9.8	GERP 1.7, phastCons 1
Regional constraint	o/e 0.64	unconstrained · MANE · 22 kb · p 6.9e-07 · regional, not allelic
Overall
CADD	34.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.0247% Middle Eastern · 1/4,041 alleles

Filtering AF 0.00175% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000884%

Overall 0.00141% 17/1,207,064 alleles · ultra-rare exomes 12/1,094,468 · genomes 5/112,596 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0247%	4,041
Admixed American	0.00658%	15,195
South Asian	0.00177%	56,532
European (non-Finnish)	0.00134%	74,476

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.Arg118Cys
Coding: c.352C>T
MANE Select: NM_001256447
dbSNP: rs1420709522
Type: single nucleotide variant
Location: chrX:153704084 (GRCh38)
Structure: AlphaFold pLDDT 84.74 · 3 PDB

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

Similar variants

BCAP31 p.Arg118His Uncertain significance ★ ⚠ same residue
BCAP31 p.Arg118= Likely benign ★ same residue
BCAP31 p.Glu245Lys Uncertain significance ★★ ⚠ same type
BCAP31 p.Gly165Arg Uncertain significance ★★ ⚠ same type
BCAP31 p.Gly239Asp Uncertain significance ★★ ⚠ same type
BCAP31 p.Ile56Val Uncertain significance ★★ ⚠ same type
BCAP31 p.Leu226Val Uncertain significance ★★ ⚠ same type
BCAP31 p.Leu40Pro 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/bcap31-p-arg118cys (accessed [today's date]).

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