Is BCAP31 p.Val237Leu (c.709G>C) pathogenic?

BCAP31 p.Val237Leu (c.709G>C) is classified Uncertain significance in BCAP31 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-07-28). AlphaMissense: likely benign (0.1168); Absent from gnomAD v4.1; Associated with severe motor and intellectual disabilities-sensorineural deafness-dystonia syndrome.

How common is BCAP31 p.Val237Leu (c.709G>C) in the general population?

BCAP31 p.Val237Leu (c.709G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BCAP31 p.Val237Leu (c.709G>C)?

AlphaMissense predicts likely benign (score 0.1168) — an in-silico prediction, not a clinical call.

BCAP31 p.Val237Leu

Q: What condition is associated with BCAP31 p.Val237Leu (c.709G>C)?

BCAP31 p.Val237Leu (c.709G>C) is associated with severe motor and intellectual disabilities-sensorineural deafness-dystonia syndrome (ClinVar).

c.709G>C · rs1557047242 · VCV2439484

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1168 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,207,477)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

severe motor and intellectual disabilities-sensorineural deafness-dystonia syndrome

Computational evidence

Protein change
AlphaMissense	0.1168	likely benign
REVEL	0.036	moderately benign-leaning
SaProt	LLR -7.65	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 0.22	GERP -0.077, phastCons 0.009
Regional constraint	o/e 0.64	unconstrained · MANE · 22 kb · p 6.9e-07 · regional, not allelic
Overall
CADD	7.667	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

No allele count reported in gnomAD v4.1 (AN 1,207,477). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: BCAP31
Protein: p.Val237Leu
Coding: c.709G>C
MANE Select: NM_001256447
dbSNP: rs1557047242
Type: single nucleotide variant
Location: chrX:153700969 (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.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.Arg31Lys Uncertain significance ★ ⚠ same condition
BCAP31 p.Asp164Glu Uncertain significance ★ ⚠ same condition
BCAP31 c.194-2A>G Pathogenic 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-val237leu (accessed [today's date]).

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