Is BSN p.Arg675Trp (c.2023C>T) pathogenic?

BSN p.Arg675Trp (c.2023C>T) is classified Uncertain significance in BSN (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-03). AlphaMissense: likely benign (0.2859); Very rare (popmax 0.00224%, sas).

How common is BSN p.Arg675Trp (c.2023C>T) in the general population?

BSN p.Arg675Trp (c.2023C>T) is very rare (popmax 0.00224%, sas) (gnomAD).

What do computational predictors say about BSN p.Arg675Trp (c.2023C>T)?

AlphaMissense predicts likely benign (score 0.2859) — an in-silico prediction, not a clinical call.

BSN p.Arg675Trp

c.2023C>T · VCV3482654

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2859 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00224%, sas)

Computational evidence

Protein change
AlphaMissense	0.2859	likely benign
REVEL	0.366	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.9	GERP 1.2, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 98 kb · p 3.9e-05 · regional, not allelic
Overall
CADD	27.4	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00224% South Asian · 2/89,294 alleles

Filtering AF 0.000545% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000431%

Overall 0.00393% 63/1,603,194 alleles · very rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.0707%	1,415
Remaining individualsnot grpmax-eligible	0.00484%	20,667
South Asiangrpmax	0.00224%	44,647
Admixed American	0.00169%	59,148
European (non-Finnish)	0.00102%	97,805

Finnish 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.Arg675Trp
Coding: c.2023C>T
MANE Select: NM_003458
Type: single nucleotide variant
Location: chr3:49651579 (GRCh38)
Gene constraint: LOEUF 0.271 · pLI 1.00 (gnomAD)
Residue 675: the 'disordered' region

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

Similar variants

BSN p.Arg675Gln Uncertain significance ★ ⚠ 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-arg675trp (accessed [today's date]).

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