Is BSN p.Arg1468Gln (c.4403G>A) pathogenic?

BSN p.Arg1468Gln (c.4403G>A) is classified Uncertain significance in BSN (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-25). AlphaMissense: likely benign (0.0755); Very rare (popmax 0.00329%, sas).

How common is BSN p.Arg1468Gln (c.4403G>A) in the general population?

BSN p.Arg1468Gln (c.4403G>A) is very rare (popmax 0.00329%, sas) (gnomAD).

What do computational predictors say about BSN p.Arg1468Gln (c.4403G>A)?

AlphaMissense predicts likely benign (score 0.0755) — an in-silico prediction, not a clinical call.

BSN p.Arg1468Gln

c.4403G>A · rs752198736 · VCV2319172

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0755 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00329%, sas)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Computational evidence

Protein change
AlphaMissense	0.0755	likely benign
REVEL	0.082	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 2.8	GERP 0.022, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 12 kb · p 3.9e-13 · regional, not allelic
Overall
CADD	19.99	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 0.00329% South Asian · 3/91,086 alleles

Filtering AF 0.000953% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000787%

Overall 0.00171% 25/1,461,810 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00329%	30,362
East Asian	0.00223%	44,886
Admixed American	0.00167%	59,992
Remaining individualsnot grpmax-eligible	0.0016%	62,478
European (non-Finnish)	0.00153%	65,556
African / African-American	0.00134%	74,860

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.Arg1468Gln
Coding: c.4403G>A
MANE Select: NM_003458
dbSNP: rs752198736
Type: single nucleotide variant
Location: chr3:49653959 (GRCh38)
Gene constraint: LOEUF 0.271 · pLI 1.00 (gnomAD)
Residue 1468: 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-arg1468gln (accessed [today's date]).

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