Is BSN p.Ala1737Ser (c.5209G>T) pathogenic?

BSN p.Ala1737Ser (c.5209G>T) is classified Uncertain significance in BSN (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-16). AlphaMissense: likely benign (0.1226); Very rare (popmax 0.000339%, nfe).

How common is BSN p.Ala1737Ser (c.5209G>T) in the general population?

BSN p.Ala1737Ser (c.5209G>T) is very rare (popmax 0.000339%, nfe) (gnomAD).

What do computational predictors say about BSN p.Ala1737Ser (c.5209G>T)?

AlphaMissense predicts likely benign (score 0.1226) — an in-silico prediction, not a clinical call.

BSN p.Ala1737Ser

c.5209G>T · VCV3482643

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1226 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000339%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Computational evidence

Protein change
AlphaMissense	0.1226	likely benign
REVEL	0.065	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 8.6	GERP 1.3, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 12 kb · p 3.9e-13 · regional, not allelic
Overall
CADD	22.2	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 0.000339% European (non-Finnish) · 4/1,180,000 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000274% 4/1,461,386 alleles · very rare

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.Ala1737Ser
Coding: c.5209G>T
MANE Select: NM_003458
Type: single nucleotide variant
Location: chr3:49654765 (GRCh38)
Gene constraint: LOEUF 0.271 · pLI 1.00 (gnomAD)

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

Similar variants

BSN p.Ala1737Gly 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-ala1737ser (accessed [today's date]).

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