Is BSND p.Tyr98fs (c.290_291dup) pathogenic?

BSND p.Tyr98fs (c.290291dup) is classified Pathogenic in BSND (ClinVar, Single submitter, 1 submitter; last evaluated 2022-04-08). Very rare (popmax 0.00133%, afr).

How common is BSND p.Tyr98fs (c.290_291dup) in the general population?

BSND p.Tyr98fs (c.290_291dup) is very rare (popmax 0.00133%, afr) (gnomAD).

BSND p.Tyr98fs

c.290_291dup · rs1557485170 · VCV1457051

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 3 of 4
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -2.4	GERP -2

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00133% African / African-American · 1/75,038 alleles

Overall 6.84e-05% 1/1,461,814 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: BSND
Protein: p.Tyr98fs
Coding: c.290_291dup
MANE Select: NM_057176
dbSNP: rs1557485170
Type: Duplication
Location: chr1:55007012 (GRCh38)
Gene constraint: LOEUF 1.03 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 53.80
Residue 98: 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.Tyr98= Conflicting classifications of pathogenicity ★ same residue
BSND p.Ala133fs Likely pathogenic ★ same type
BSND p.Ala186fs Pathogenic ★ same type
BSND p.Ile49fs Pathogenic ★ same type
BSND p.Trp157fs Likely pathogenic ★ same type
BSND p.Val162fs Likely pathogenic ★ same type
BSND c.-42_-1dup Uncertain significance ★ same type
BSND c.*305_*311dup Likely benign ★ 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-tyr98fs (accessed [today's date]).

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