Is BSND p.Arg8Gly (c.22C>G) pathogenic?

BSND p.Arg8Gly (c.22C>G) is classified Pathogenic in BSND (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-10). AlphaMissense: likely pathogenic (0.9338); Absent from gnomAD v4.1.

How common is BSND p.Arg8Gly (c.22C>G) in the general population?

BSND p.Arg8Gly (c.22C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BSND p.Arg8Gly (c.22C>G)?

AlphaMissense predicts likely pathogenic (score 0.9338) — an in-silico prediction, not a clinical call.

BSND p.Arg8Gly

c.22C>G · rs74315285 · VCV2910107

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9338 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9338	likely pathogenic ✓ concordant with ClinVar · top 3% in BSND
REVEL	0.841	moderately pathogenic-leaning
SaProt	LLR -7.91	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP 1.4, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 9,438 bp · p 0.065 · regional, not allelic
Overall
CADD	27.2	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

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: BSND
Protein: p.Arg8Gly
Coding: c.22C>G
MANE Select: NM_057176
dbSNP: rs74315285
Type: single nucleotide variant
Location: chr1:54999208 (GRCh38)
Gene constraint: LOEUF 1.03 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 53.80
Residue 8: a UniProt-annotated variant site (in barts4a); a UniProt-annotated variant site (in barts4a; fails to activate clcnka and clcnkb channels); a UniProt-annotated variant site (in barts4a; fails to activate clcnka and clcnkb channels; loss of channel conductance); the 'regulates channel membrane trafficking and ion conductance' region

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

Similar variants

BSND p.Arg8Trp Pathogenic/Likely pathogenic ★★ same residue
BSND p.Arg8Gln Conflicting classifications of pathogenicity ★ ⚠ same residue
BSND p.Arg8= Likely benign ★ same residue
BSND p.Arg8Leu Pathogenic same residue
BSND c.178-2A>C Likely pathogenic ★★ same type
BSND c.272+1G>T Pathogenic/Likely pathogenic ★★ same type
BSND p.Gln95Ter Pathogenic/Likely pathogenic ★★ same type
BSND p.Glu148Ter Pathogenic/Likely pathogenic ★★ 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/bsnd-p-arg8gly (accessed [today's date]).

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