Is BSND p.Val154Ile (c.460G>A) pathogenic?

BSND p.Val154Ile (c.460G>A) is classified Uncertain significance in BSND (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-23). AlphaMissense: likely benign (0.0802); Ultra-rare (popmax 0.0167%, amr).

How common is BSND p.Val154Ile (c.460G>A) in the general population?

BSND p.Val154Ile (c.460G>A) is ultra-rare (popmax 0.0167%, amr) (gnomAD).

What do computational predictors say about BSND p.Val154Ile (c.460G>A)?

AlphaMissense predicts likely benign (score 0.0802) — an in-silico prediction, not a clinical call.

BSND p.Val154Ile

c.460G>A · rs529780817 · VCV2430464

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0802 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0167%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0802	likely benign
REVEL	0.081	moderately benign-leaning
SaProt	LLR -6.96	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 -2.2	GERP -2.8
Regional constraint	o/e 0.91	unconstrained · MANE · 9,438 bp · p 0.065 · regional, not allelic
Overall
CADD	0.592	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 0.0167% Admixed American · 10/60,022 alleles

Filtering AF 0.00899% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00681%

Overall 0.00161% 26/1,614,206 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0167%	6,002
South Asian	0.00659%	15,180
East Asian	0.00223%	44,878
Remaining individualsnot grpmax-eligible	0.0016%	62,510
African / African-American	0.00133%	75,050
European (non-Finnish)	0.000593%	168,577

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.Val154Ile
Coding: c.460G>A
MANE Select: NM_057176
dbSNP: rs529780817
Type: single nucleotide variant
Location: chr1:55007184 (GRCh38)
Gene constraint: LOEUF 1.03 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 53.80
Residue 154: 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 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
BSND p.Gly10Ser 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-val154ile (accessed [today's date]).

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