Is BCAP31 p.Leu21Pro (c.62T>C) pathogenic?

BCAP31 p.Leu21Pro (c.62T>C) is classified Uncertain significance in BCAP31 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-10-09). AlphaMissense: likely pathogenic (0.8722); Absent from gnomAD v4.1.

How common is BCAP31 p.Leu21Pro (c.62T>C) in the general population?

BCAP31 p.Leu21Pro (c.62T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BCAP31 p.Leu21Pro (c.62T>C)?

AlphaMissense predicts likely pathogenic (score 0.8722) — an in-silico prediction, not a clinical call.

BCAP31 p.Leu21Pro

c.62T>C · rs2148385953 · VCV1304071

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8722 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8722	likely pathogenic
REVEL	0.68	pathogenic-leaning
SaProt	LLR -13.78	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.6, phastCons 1
Regional constraint	o/e 0.64	unconstrained · MANE · 22 kb · p 6.9e-07 · regional, not allelic
Overall
CADD	28.5	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: BCAP31
Protein: p.Leu21Pro
Coding: c.62T>C
MANE Select: NM_001256447
dbSNP: rs2148385953
Type: single nucleotide variant
Location: chrX:153723183 (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.Arg118Cys Uncertain significance ★★ ⚠ same type
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
BCAP31 p.Lys30Arg 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-leu21pro (accessed [today's date]).

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