Is BCAP31 p.Asn133Ser (c.398A>G) pathogenic?

BCAP31 p.Asn133Ser (c.398A>G) is classified Conflicting classifications of pathogenicity in BCAP31 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2026-01-19). AlphaMissense: likely benign (0.0862); Ultra-rare (popmax 0.0299%, sas); Associated with Inborn genetic diseases.

What condition is associated with BCAP31 p.Asn133Ser (c.398A>G)?

BCAP31 p.Asn133Ser (c.398A>G) is associated with Inborn genetic diseases (ClinVar).

How common is BCAP31 p.Asn133Ser (c.398A>G) in the general population?

BCAP31 p.Asn133Ser (c.398A>G) is ultra-rare (popmax 0.0299%, sas) (gnomAD).

What do computational predictors say about BCAP31 p.Asn133Ser (c.398A>G)?

AlphaMissense predicts likely benign (score 0.0862) — an in-silico prediction, not a clinical call.

BCAP31 p.Asn133Ser

c.398A>G · rs199876065 · VCV2177356

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0862 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0299%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0862	likely benign
REVEL	0.223	benign-leaning
SaProt	LLR -7.51	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 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	20.1	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 0.0299% South Asian · 17/56,856 alleles

Filtering AF 0.019% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0156%

Overall 0.0102% 123/1,210,109 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0299%	3,344
Remaining individualsnot grpmax-eligible	0.0231%	4,326
European (non-Finnish)	0.0104%	9,624
East Asian	0.00296%	33,765
African / African-American	0.00174%	57,408

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.Asn133Ser
Coding: c.398A>G
MANE Select: NM_001256447
dbSNP: rs199876065
Type: single nucleotide variant
Location: chrX:153704038 (GRCh38)
Structure: AlphaFold pLDDT 84.74 · 3 PDB

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

BCAP31 p.Glu245Lys Uncertain significance ★★ ⚠ same condition
BCAP31 p.Gly165Arg Uncertain significance ★★ ⚠ same condition
BCAP31 p.Ile56Val Uncertain significance ★★ ⚠ same condition
BCAP31 p.Leu226Val Uncertain significance ★★ ⚠ same condition
BCAP31 p.Lys30Arg Uncertain significance ★★ ⚠ same condition
BCAP31 p.Ter247Gln Likely pathogenic ★ same condition
BCAP31 c.-44-276A>G Uncertain significance ★ same condition
BCAP31 c.-44-288G>T Uncertain significance ★ same condition

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-asn133ser (accessed [today's date]).

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