Is BSND p.Leu243Pro (c.728T>C) pathogenic?

BSND p.Leu243Pro (c.728T>C) is classified Uncertain significance in BSND (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-03). AlphaMissense: ambiguous (0.3622); Very rare (popmax 0.00223%, eas); Associated with Inborn genetic diseases.

What condition is associated with BSND p.Leu243Pro (c.728T>C)?

BSND p.Leu243Pro (c.728T>C) is associated with Inborn genetic diseases (ClinVar).

How common is BSND p.Leu243Pro (c.728T>C) in the general population?

BSND p.Leu243Pro (c.728T>C) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about BSND p.Leu243Pro (c.728T>C)?

AlphaMissense predicts ambiguous (score 0.3622) — an in-silico prediction, not a clinical call.

BSND p.Leu243Pro

c.728T>C · VCV3482675

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3622 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3622	ambiguous
REVEL	0.495	indeterminate
SaProt	LLR -6.54	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 1.6, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 9,438 bp · p 0.065 · regional, not allelic
Overall
CADD	24.4	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 0.00223% East Asian · 1/44,882 alleles

Overall 0.000137% 2/1,461,884 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,882
Remaining individualsnot grpmax-eligible	0.0016%	62,508

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.Leu243Pro
Coding: c.728T>C
MANE Select: NM_057176
Type: single nucleotide variant
Location: chr1:55008393 (GRCh38)
Gene constraint: LOEUF 1.03 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 53.80
Residue 243: 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

Disease context

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

Similar variants

BSND p.Leu243Arg 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-leu243pro (accessed [today's date]).

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