Is BSN p.Arg1269Cys (c.3805C>T) pathogenic?

BSN p.Arg1269Cys (c.3805C>T) is classified Uncertain significance in BSN (ClinVar, Single submitter, 1 submitter; last evaluated 2021-07-26). AlphaMissense: likely benign (0.1939); Very rare (popmax 0.00602%, nfe).

How common is BSN p.Arg1269Cys (c.3805C>T) in the general population?

BSN p.Arg1269Cys (c.3805C>T) is very rare (popmax 0.00602%, nfe) (gnomAD).

What do computational predictors say about BSN p.Arg1269Cys (c.3805C>T)?

AlphaMissense predicts likely benign (score 0.1939) — an in-silico prediction, not a clinical call.

BSN p.Arg1269Cys

c.3805C>T · rs151276316 · VCV2239262

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1939 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00602%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Computational evidence

Protein change
AlphaMissense	0.1939	likely benign
REVEL	0.137	moderately benign-leaning
⇒ AlphaMissense and REVEL both call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.3	GERP -0.1, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 12 kb · p 3.9e-13 · regional, not allelic
Overall
CADD	27.1	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 0.00602% European (non-Finnish) · 71/1,179,664 alleles

Filtering AF 0.00486% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00447%

Overall 0.00477% 77/1,613,004 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00602%	16,615
Admixed American	0.00334%	29,970
Remaining individualsnot grpmax-eligible	0.0032%	31,228
East Asian	0.00223%	44,890
African / African-American	0.00133%	74,916

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: BSN
Protein: p.Arg1269Cys
Coding: c.3805C>T
MANE Select: NM_003458
dbSNP: rs151276316
Type: single nucleotide variant
Location: chr3:49653361 (GRCh38)
Gene constraint: LOEUF 0.271 · pLI 1.00 (gnomAD)

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

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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/bsn-p-arg1269cys (accessed [today's date]).

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