Is BSN p.Arg3774Cys (c.11320C>T) pathogenic?

BSN p.Arg3774Cys (c.11320C>T) is classified Uncertain significance in BSN (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-14). AlphaMissense: likely benign (0.188); Very rare (popmax 0.00668%, eas).

How common is BSN p.Arg3774Cys (c.11320C>T) in the general population?

BSN p.Arg3774Cys (c.11320C>T) is very rare (popmax 0.00668%, eas) (gnomAD).

What do computational predictors say about BSN p.Arg3774Cys (c.11320C>T)?

AlphaMissense predicts likely benign (score 0.188) — an in-silico prediction, not a clinical call.

BSN p.Arg3774Cys

c.11320C>T · VCV3482612

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.188 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00668%, eas)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Computational evidence

Protein change
AlphaMissense	0.188	likely benign
REVEL	0.138	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 3.7	GERP 2.2, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 12 kb · p 3.9e-13 · regional, not allelic
Overall
CADD	24.7	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 0.00668% East Asian · 3/44,902 alleles

Filtering AF 0.00177% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000891%

Overall 0.000682% 11/1,612,748 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00668%	14,967
Remaining individualsnot grpmax-eligible	0.0016%	62,442
African / African-American	0.00133%	74,950
South Asian	0.0011%	91,088
European (non-Finnish)	0.000424%	235,994

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.Arg3774Cys
Coding: c.11320C>T
MANE Select: NM_003458
Type: single nucleotide variant
Location: chr3:49663478 (GRCh38)
Gene constraint: LOEUF 0.271 · pLI 1.00 (gnomAD)
Residue 3774: the 'disordered' region

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-arg3774cys (accessed [today's date]).

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