Is BVES p.Ser201Cys (c.602C>G) pathogenic?

BVES p.Ser201Cys (c.602C>G) is classified Likely pathogenic in BVES (ClinVar, Single submitter, 1 submitter; last evaluated 2021-07-08). AlphaMissense: likely pathogenic (0.989); Very rare (popmax 0.00446%, eas).

How common is BVES p.Ser201Cys (c.602C>G) in the general population?

BVES p.Ser201Cys (c.602C>G) is very rare (popmax 0.00446%, eas) (gnomAD).

What do computational predictors say about BVES p.Ser201Cys (c.602C>G)?

AlphaMissense predicts likely pathogenic (score 0.989) — an in-silico prediction, not a clinical call.

BVES p.Ser201Cys

c.602C>G · rs869025337 · VCV1686644

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.989 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00446%, eas)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.989	likely pathogenic ✓ concordant with ClinVar · top 7% in BVES
REVEL	0.75	pathogenic-leaning
SaProt	LLR -13.50	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 12	GERP 2.9, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 32 kb · p 0.55 · regional, not allelic
Overall
CADD	29.1	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 0.00446% East Asian · 2/44,816 alleles

Filtering AF 0.00074% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000277%

Overall 0.000137% 2/1,460,688 alleles · very rare

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: BVES
Protein: p.Ser201Cys
Coding: c.602C>G
MANE Select: NM_001199563
dbSNP: rs869025337
Type: single nucleotide variant
Location: chr6:105124593 (GRCh38)
Gene constraint: LOEUF 0.915 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.08
Residue 201: a UniProt-annotated variant site (in lgmdr25; reduces membrane localization of popdc1 and popdc2; decreases by 50% affinity for camp; disrupts enhancement of kckn2 surface expression; increases kckn2 outward currents; no effect on total protein levels)

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

Similar variants

POPDC1 p.Ser201Phe Likely pathogenic ★★ same residue
POP1 p.Gln778Ter Pathogenic/Likely pathogenic ★★ same type
POP1 p.Val696Asp Likely pathogenic ★★ ⚠ same type
POPDC1 p.Arg88Ter Pathogenic/Likely pathogenic ★★ same type
POP1 p.Ala1011Thr Uncertain significance ★★ ⚠ same type
POP1 p.Ala166Pro Uncertain significance ★★ ⚠ same type
POP1 p.Ala44Pro Uncertain significance ★★ ⚠ same type
POP1 p.Ala497Val 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/bves-p-ser201cys (accessed [today's date]).

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