Is BSND p.Pro308Leu (c.923C>T) pathogenic?

BSND p.Pro308Leu (c.923C>T) is classified Uncertain significance in BSND (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-08-02). AlphaMissense: likely benign (0.1258); Ultra-rare (popmax 0.0253%, afr); Associated with Inborn genetic diseases.

What condition is associated with BSND p.Pro308Leu (c.923C>T)?

BSND p.Pro308Leu (c.923C>T) is associated with Inborn genetic diseases (ClinVar).

How common is BSND p.Pro308Leu (c.923C>T) in the general population?

BSND p.Pro308Leu (c.923C>T) is ultra-rare (popmax 0.0253%, afr) (gnomAD).

What do computational predictors say about BSND p.Pro308Leu (c.923C>T)?

AlphaMissense predicts likely benign (score 0.1258) — an in-silico prediction, not a clinical call.

BSND p.Pro308Leu

c.923C>T · rs201583148 · VCV1706717

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1258 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0253%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1258	likely benign
REVEL	0.297	indeterminate
SaProt	LLR -5.88	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.2	GERP 1.5, phastCons 0.95
Regional constraint	o/e 0.91	unconstrained · MANE · 9,438 bp · p 0.065 · regional, not allelic
Overall
CADD	18.42	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 0.0253% African / African-American · 19/75,024 alleles

Filtering AF 0.0165% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0137%

Overall 0.00279% 45/1,614,142 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0253%	3,949
Remaining individualsnot grpmax-eligible	0.0048%	20,837
Admixed American	0.00333%	30,011
South Asian	0.0022%	45,542
Finnishnot grpmax-eligible	0.00156%	64,028
European (non-Finnish)	0.00153%	65,557

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.Pro308Leu
Coding: c.923C>T
MANE Select: NM_057176
dbSNP: rs201583148
Type: single nucleotide variant
Location: chr1:55008588 (GRCh38)
Gene constraint: LOEUF 1.03 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 53.80
Residue 308: 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

Disease context

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

Similar variants

BSND p.Pro308= Likely benign ★ 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-pro308leu (accessed [today's date]).

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