Is BSND p.Arg129His (c.386G>A) pathogenic?

BSND p.Arg129His (c.386G>A) is classified Uncertain significance in BSND (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-08-03). AlphaMissense: likely benign (0.0659); Very rare (popmax 0.00167%, amr).

How common is BSND p.Arg129His (c.386G>A) in the general population?

BSND p.Arg129His (c.386G>A) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about BSND p.Arg129His (c.386G>A)?

AlphaMissense predicts likely benign (score 0.0659) — an in-silico prediction, not a clinical call.

BSND p.Arg129His

c.386G>A · rs367549117 · VCV2180512

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0659 · 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	0.0659	likely benign
REVEL	0.078	moderately benign-leaning
SaProt	LLR -6.58	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 0.27	GERP -2.8
Regional constraint	o/e 0.91	unconstrained · MANE · 9,438 bp · p 0.065 · regional, not allelic
Overall
CADD	5.508	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 · 1/60,004 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9e-05%

Overall 0.000496% 8/1,614,062 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	60,004
African / African-American	0.00133%	74,908
South Asian	0.0011%	91,082
European (non-Finnish)	0.000424%	236,009

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.Arg129His
Coding: c.386G>A
MANE Select: NM_057176
dbSNP: rs367549117
Type: single nucleotide variant
Location: chr1:55007110 (GRCh38)
Gene constraint: LOEUF 1.03 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 53.80
Residue 129: 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)

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

Similar variants

BSND p.Arg129Cys Uncertain significance ★ ⚠ same residue
BSND p.Arg129Gly Uncertain significance ★ ⚠ same residue
BSND p.Arg129= Likely benign ★ 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

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-arg129his (accessed [today's date]).

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