Is BSND p.Ala192Asp (c.575C>A) pathogenic?

BSND p.Ala192Asp (c.575C>A) is classified Uncertain significance in BSND (ClinVar, Single submitter, 1 submitter; last evaluated 2019-09-05). AlphaMissense: likely pathogenic (0.7876); Very rare (popmax 0.00133%, afr).

How common is BSND p.Ala192Asp (c.575C>A) in the general population?

BSND p.Ala192Asp (c.575C>A) is very rare (popmax 0.00133%, afr) (gnomAD).

What do computational predictors say about BSND p.Ala192Asp (c.575C>A)?

AlphaMissense predicts likely pathogenic (score 0.7876) — an in-silico prediction, not a clinical call.

BSND p.Ala192Asp

c.575C>A · rs770850590 · VCV389251

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7876 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.7876	likely pathogenic · top 7% in BSND
REVEL	0.423	indeterminate
SaProt	LLR -6.46	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	Δ0.27	acceptor gain · deltas
Pangolin	Δ0.30	gain · loss 0.11 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 4.8	GERP 1.6, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 9,438 bp · p 0.065 · regional, not allelic
Overall
CADD	33.0	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

Grpmax group 0.00133% African / African-American · 1/75,056 alleles

Overall 6.84e-05% 1/1,461,850 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.Ala192Asp
Coding: c.575C>A
MANE Select: NM_057176
dbSNP: rs770850590
Type: single nucleotide variant
Location: chr1:55008240 (GRCh38)
Gene constraint: LOEUF 1.03 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 53.80
Residue 192: 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.Ala192= 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
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-ala192asp (accessed [today's date]).

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