Is BSN p.Arg1335Gln (c.4004G>A) pathogenic?

BSN p.Arg1335Gln (c.4004G>A) is classified Uncertain significance in BSN (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-08). AlphaMissense: likely benign (0.1031); Very rare (popmax 0.00297%, nfe).

How common is BSN p.Arg1335Gln (c.4004G>A) in the general population?

BSN p.Arg1335Gln (c.4004G>A) is very rare (popmax 0.00297%, nfe) (gnomAD).

What do computational predictors say about BSN p.Arg1335Gln (c.4004G>A)?

AlphaMissense predicts likely benign (score 0.1031) — an in-silico prediction, not a clinical call.

BSN p.Arg1335Gln

c.4004G>A · rs547695155 · VCV3135255

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1031 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00297%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Computational evidence

Protein change
AlphaMissense	0.1031	likely benign
REVEL	0.118	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 7.5	GERP 2.3, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 12 kb · p 3.9e-13 · regional, not allelic
Overall
CADD	27.5	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 0.00297% European (non-Finnish) · 35/1,179,974 alleles

Filtering AF 0.00215% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00191%

Overall 0.00248% 40/1,613,884 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0048%	20,836
European (non-Finnish)grpmax	0.00297%	33,714
East Asian	0.00223%	44,876
South Asian	0.0011%	91,064

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Arg1335Gln
Coding: c.4004G>A
MANE Select: NM_003458
dbSNP: rs547695155
Type: single nucleotide variant
Location: chr3:49653560 (GRCh38)
Gene constraint: LOEUF 0.271 · pLI 1.00 (gnomAD)
Residue 1335: the 'disordered' region

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

Similar variants

BSN p.Arg1335Ter Conflicting classifications of pathogenicity ★ ⚠ same residue
BSN p.Ala1623Thr Uncertain significance ★★ ⚠ same type
BSN p.Ala2329Val Uncertain significance ★★ ⚠ same type
BSN p.Ala2475Pro Uncertain significance ★★ ⚠ same type
BSN p.Arg1145Trp Uncertain significance ★★ ⚠ same type
BSN p.Arg2221His Uncertain significance ★★ ⚠ same type
BSN p.Arg3229Gln Uncertain significance ★★ same type
BSN p.Arg976His Uncertain significance ★★ same type

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-arg1335gln (accessed [today's date]).

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