Is BSND p.Arg232Ser (c.696G>T) pathogenic?

BSND p.Arg232Ser (c.696G>T) is classified Uncertain significance in BSND (ClinVar, No assertion criteria, 1 submitter). AlphaMissense: likely benign (0.1326); Very rare (popmax 0.00167%, amr).

How common is BSND p.Arg232Ser (c.696G>T) in the general population?

BSND p.Arg232Ser (c.696G>T) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about BSND p.Arg232Ser (c.696G>T)?

AlphaMissense predicts likely benign (score 0.1326) — an in-silico prediction, not a clinical call.

BSND p.Arg232Ser

c.696G>T · rs886046424 · VCV1050061

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1326 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1326	likely benign
REVEL	0.145	moderately benign-leaning
SaProt	LLR -4.68	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 1.2	GERP -0.59, phastCons 0.006
Regional constraint	o/e 0.91	unconstrained · MANE · 9,438 bp · p 0.065 · regional, not allelic
Overall
CADD	9.228	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

Grpmax group 0.00167% Admixed American · 1/60,032 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000205% 3/1,461,892 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	60,032
European (non-Finnish)	0.000169%	590,023

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: BSND
Protein: p.Arg232Ser
Coding: c.696G>T
MANE Select: NM_057176
dbSNP: rs886046424
Type: single nucleotide variant
Location: chr1:55008361 (GRCh38)
Gene constraint: LOEUF 1.03 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 53.80
Residue 232: a UniProt-annotated variant site (in barts4a); a UniProt-annotated variant site (in barts4a; loss of clcnka and clcnkb channel conductance); a UniProt-annotated variant site (in barts4a; abolishes the preferential sorting at the basolateral membrane domain; no effect on ion conductance); the 'disordered' region

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

Similar variants

BSND p.Arg232= Conflicting classifications of pathogenicity ★ same residue
BSND c.178-2A>C Likely pathogenic ★★ same type
BSND c.272+1G>T Pathogenic/Likely pathogenic ★★ same type
BSND p.Arg8Trp Pathogenic/Likely pathogenic ★★ same type
BSND p.Gln95Ter Pathogenic/Likely pathogenic ★★ same type
BSND p.Glu148Ter Pathogenic/Likely pathogenic ★★ same type
BSND p.Glu4Ter Pathogenic ★★ same type
BSND p.Glu88Ter 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-arg232ser (accessed [today's date]).

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