Is BSND p.Glu172Asp (c.516A>T) pathogenic?

BSND p.Glu172Asp (c.516A>T) is classified Conflicting classifications of pathogenicity in BSND (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2025-07-15). AlphaMissense: likely benign (0.1106); Ultra-rare (popmax 0.0956%, sas); Associated with Inborn genetic diseases.

What condition is associated with BSND p.Glu172Asp (c.516A>T)?

BSND p.Glu172Asp (c.516A>T) is associated with Inborn genetic diseases (ClinVar).

How common is BSND p.Glu172Asp (c.516A>T) in the general population?

BSND p.Glu172Asp (c.516A>T) is ultra-rare (popmax 0.0956%, sas) (gnomAD).

What do computational predictors say about BSND p.Glu172Asp (c.516A>T)?

AlphaMissense predicts likely benign (score 0.1106) — an in-silico prediction, not a clinical call.

BSND p.Glu172Asp

c.516A>T · rs532738229 · VCV2139153

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.1106 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0956%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1106	likely benign
REVEL	0.043	moderately benign-leaning
SaProt	LLR -6.32	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.35	GERP -2.5
Regional constraint	o/e 0.91	unconstrained · MANE · 9,438 bp · p 0.065 · regional, not allelic
Overall
CADD	4.072	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 0.0956% South Asian · 87/90,990 alleles

Filtering AF 0.0794% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0734%

Overall 0.0059% 95/1,610,008 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0956%	1,046
Middle Eastern	0.0331%	3,020
Remaining individualsnot grpmax-eligible	0.00482%	20,763
Admixed American	0.00167%	59,876
European (non-Finnish)	0.00017%	588,575

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.Glu172Asp
Coding: c.516A>T
MANE Select: NM_057176
dbSNP: rs532738229
Type: single nucleotide variant
Location: chr1:55007240 (GRCh38)
Gene constraint: LOEUF 1.03 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 53.80
Residue 172: 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.Glu172Lys 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-glu172asp (accessed [today's date]).

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