Is BSND p.Ala65Asp (c.194C>A) pathogenic?

BSND p.Ala65Asp (c.194C>A) is classified Uncertain significance in BSND (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-29). AlphaMissense: likely pathogenic (0.5679); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with BSND p.Ala65Asp (c.194C>A)?

BSND p.Ala65Asp (c.194C>A) is associated with Inborn genetic diseases (ClinVar).

How common is BSND p.Ala65Asp (c.194C>A) in the general population?

BSND p.Ala65Asp (c.194C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BSND p.Ala65Asp (c.194C>A)?

AlphaMissense predicts likely pathogenic (score 0.5679) — an in-silico prediction, not a clinical call.

BSND p.Ala65Asp

c.194C>A · rs1384083595 · VCV2607747

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5679 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.5679	likely pathogenic
REVEL	0.49	indeterminate
SaProt	LLR -5.98	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.2, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 9,438 bp · p 0.065 · regional, not allelic
Overall
CADD	25.2	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: BSND
Protein: p.Ala65Asp
Coding: c.194C>A
MANE Select: NM_057176
dbSNP: rs1384083595
Type: single nucleotide variant
Location: chr1:55005038 (GRCh38)
Gene constraint: LOEUF 1.03 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 53.80
Residue 65: a UniProt-annotated variant site (in barts4a); a UniProt-annotated variant site (in barts4a; loss of clcnka and clcnkb channel conductance); the 'regulates channel membrane trafficking and ion conductance' region

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

BSND p.Ala65Thr Uncertain significance ★ ⚠ same residue
BSND p.Ala106Val Uncertain significance ★★ ⚠ same condition
BSND p.Ala160Ser Uncertain significance ★★ ⚠ same condition
BSND p.Ala246Val Uncertain significance ★★ ⚠ same condition
BSND p.Arg30Gln Uncertain significance ★★ ⚠ same condition
BSND p.Asp236Asn Uncertain significance ★★ ⚠ same condition
BSND p.Glu287Ter Uncertain significance ★★ same condition
BSND p.Glu292Lys Uncertain significance ★★ ⚠ same condition

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-ala65asp (accessed [today's date]).

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