Is BSND p.Arg269Gln (c.806G>A) pathogenic?

BSND p.Arg269Gln (c.806G>A) is classified Conflicting classifications of pathogenicity in BSND (ClinVar, Conflicting submitters, 6 submitters; last evaluated 2025-03-03). AlphaMissense: likely benign (0.0627); Rare (popmax 0.247%, mid); Associated with Inborn genetic diseases.

What condition is associated with BSND p.Arg269Gln (c.806G>A)?

BSND p.Arg269Gln (c.806G>A) is associated with Inborn genetic diseases (ClinVar).

How common is BSND p.Arg269Gln (c.806G>A) in the general population?

BSND p.Arg269Gln (c.806G>A) is rare (popmax 0.247%, mid) (gnomAD).

What do computational predictors say about BSND p.Arg269Gln (c.806G>A)?

AlphaMissense predicts likely benign (score 0.0627) — an in-silico prediction, not a clinical call.

BSND p.Arg269Gln

c.806G>A · rs199832638 · VCV504521

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 6 submitters

AlphaMissense

likely benign

0.0627 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.247%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0627	likely benign
REVEL	0.232	benign-leaning
SaProt	LLR -5.96	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 -11	GERP -2.6
Regional constraint	o/e 0.91	unconstrained · MANE · 9,438 bp · p 0.065 · regional, not allelic
Overall
CADD	0.001	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 0.247% Middle Eastern · 15/6,084 alleles

Filtering AF 0.152% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.123%

Overall 0.0139% 224/1,614,042 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.247%	406
Remaining individualsnot grpmax-eligible	0.016%	6,248
European (non-Finnish)	0.0148%	6,743
South Asian	0.0121%	8,280
Admixed American	0.0117%	8,570
African / African-American	0.00801%	12,489

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.Arg269Gln
Coding: c.806G>A
MANE Select: NM_057176
dbSNP: rs199832638
Type: single nucleotide variant
Location: chr1:55008471 (GRCh38)
Gene constraint: LOEUF 1.03 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 53.80
Residue 269: 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.Arg269Trp Conflicting classifications of pathogenicity ★ ⚠ 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-arg269gln (accessed [today's date]).

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