Is BVES p.Lys178Gln (c.532A>C) pathogenic?

BVES p.Lys178Gln (c.532A>C) is classified Uncertain significance in BVES (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-16). AlphaMissense: likely benign (0.2128); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with BVES p.Lys178Gln (c.532A>C)?

BVES p.Lys178Gln (c.532A>C) is associated with Inborn genetic diseases (ClinVar).

How common is BVES p.Lys178Gln (c.532A>C) in the general population?

BVES p.Lys178Gln (c.532A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BVES p.Lys178Gln (c.532A>C)?

AlphaMissense predicts likely benign (score 0.2128) — an in-silico prediction, not a clinical call.

BVES p.Lys178Gln

c.532A>C · VCV3262340

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2128 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2128	likely benign
REVEL	0.15	moderately benign-leaning
SaProt	LLR -5.05	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 2.9, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 32 kb · p 0.55 · regional, not allelic
Overall
CADD	25.1	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: BVES
Protein: p.Lys178Gln
Coding: c.532A>C
MANE Select: NM_001199563
Type: single nucleotide variant
Location: chr6:105125398 (GRCh38)
Gene constraint: LOEUF 0.915 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.08
Residue 178: the 'required for interaction with kcnk2' region

Full BVES 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

POP1 p.Ala1011Thr Uncertain significance ★★ ⚠ same condition
POP1 p.Ala166Pro Uncertain significance ★★ ⚠ same condition
POP1 p.Ala44Pro Uncertain significance ★★ ⚠ same condition
POP1 p.Ala497Val Uncertain significance ★★ ⚠ same condition
POP1 p.Ala673Val Uncertain significance ★★ ⚠ same condition
POP1 p.Ala721Thr Uncertain significance ★★ ⚠ same condition
POP1 p.Ala942Pro Uncertain significance ★★ ⚠ same condition
POP1 p.Arg188Trp 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/bves-p-lys178gln (accessed [today's date]).

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