Is BSN p.Arg2712Cys (c.8134C>T) pathogenic?

BSN p.Arg2712Cys (c.8134C>T) is classified Uncertain significance in BSN (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-01). AlphaMissense: likely benign (0.0972); Very rare (popmax 0.00531%, nfe).

How common is BSN p.Arg2712Cys (c.8134C>T) in the general population?

BSN p.Arg2712Cys (c.8134C>T) is very rare (popmax 0.00531%, nfe) (gnomAD).

What do computational predictors say about BSN p.Arg2712Cys (c.8134C>T)?

AlphaMissense predicts likely benign (score 0.0972) — an in-silico prediction, not a clinical call.

BSN p.Arg2712Cys

c.8134C>T · VCV4216489

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0972 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00531%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Computational evidence

Protein change
AlphaMissense	0.0972	likely benign
REVEL	0.11	moderately benign-leaning
⇒ AlphaMissense and REVEL both call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.39 · evaluated, not missing
Constraint at this position
Conservation	phyloP 4.1	GERP 0.32, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 12 kb · p 3.9e-13 · regional, not allelic
Overall
CADD	25.8	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 0.00531% European (non-Finnish) · 61/1,149,070 alleles

Filtering AF 0.00421% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00382%

Overall 0.00476% 67/1,407,014 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00531%	18,837
Remaining individualsnot grpmax-eligible	0.00499%	20,028
South Asian	0.00244%	41,059
Finnishnot grpmax-eligible	0.00164%	60,874

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.Arg2712Cys
Coding: c.8134C>T
MANE Select: NM_003458
Type: single nucleotide variant
Location: chr3:49657690 (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-arg2712cys (accessed [today's date]).

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