Is BCAP31 p.Arg31Lys (c.92G>A) pathogenic?

BCAP31 p.Arg31Lys (c.92G>A) is classified Uncertain significance in BCAP31 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-03). AlphaMissense: likely benign (0.3162); Absent from gnomAD v4.1; Associated with severe motor and intellectual disabilities-sensorineural deafness-dystonia syndrome.

How common is BCAP31 p.Arg31Lys (c.92G>A) in the general population?

BCAP31 p.Arg31Lys (c.92G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BCAP31 p.Arg31Lys (c.92G>A)?

AlphaMissense predicts likely benign (score 0.3162) — an in-silico prediction, not a clinical call.

BCAP31 p.Arg31Lys

Q: What condition is associated with BCAP31 p.Arg31Lys (c.92G>A)?

BCAP31 p.Arg31Lys (c.92G>A) is associated with severe motor and intellectual disabilities-sensorineural deafness-dystonia syndrome (ClinVar).

c.92G>A · VCV4533214

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3162 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

severe motor and intellectual disabilities-sensorineural deafness-dystonia syndrome

Computational evidence

Protein change
AlphaMissense	0.3162	likely benign
REVEL	0.167	moderately benign-leaning
SaProt	LLR -4.69	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.89	donor loss · deltas
Pangolin	Δ0.71	loss · gain 0.06 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 7.6	GERP 0.55, phastCons 1
Regional constraint	o/e 0.64	unconstrained · MANE · 22 kb · p 6.9e-07 · regional, not allelic
Overall
CADD	32.0	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

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.Arg31Lys
Coding: c.92G>A
MANE Select: NM_001256447
Type: single nucleotide variant
Location: chrX:153723153 (GRCh38)
Structure: AlphaFold pLDDT 84.74 · 3 PDB

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

Disease context

severe motor and intellectual disabilities-sensorineural deafness-dystonia syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

BCAP31 p.Arg31Ter Pathogenic ★ same residue
BCAP31 p.Gly239Asp Uncertain significance ★★ ⚠ same condition
BCAP31 c.341+2T>G Pathogenic ★ same condition
BCAP31 p.Gln139Ter Pathogenic ★ same condition
BCAP31 p.Gln156Ter Likely pathogenic ★ same condition
BCAP31 p.Ala106Val Uncertain significance ★ ⚠ same condition
BCAP31 p.Asp164Glu Uncertain significance ★ ⚠ same condition
BCAP31 p.Val237Leu 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-arg31lys (accessed [today's date]).

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