Is BSN p.Ala1273Ser (c.3817G>T) pathogenic?

BSN p.Ala1273Ser (c.3817G>T) is classified Uncertain significance in BSN (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-17). AlphaMissense: likely benign (0.0834); Ultra-rare (popmax 0.0364%, nfe).

How common is BSN p.Ala1273Ser (c.3817G>T) in the general population?

BSN p.Ala1273Ser (c.3817G>T) is ultra-rare (popmax 0.0364%, nfe) (gnomAD).

What do computational predictors say about BSN p.Ala1273Ser (c.3817G>T)?

AlphaMissense predicts likely benign (score 0.0834) — an in-silico prediction, not a clinical call.

BSN p.Ala1273Ser

c.3817G>T · VCV3261923

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0834 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0364%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Computational evidence

Protein change
AlphaMissense	0.0834	likely benign
REVEL	0.089	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 4.5	GERP 1.1, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 12 kb · p 3.9e-13 · regional, not allelic
Overall
CADD	15.97	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 0.0364% European (non-Finnish) · 429/1,179,900 alleles

Filtering AF 0.0335% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0323%

Overall 0.0274% 442/1,613,460 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0364%	2,750
Remaining individualsnot grpmax-eligible	0.0144%	6,941
African / African-American	0.004%	24,974
Finnishnot grpmax-eligible	0.00157%	63,680

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.Ala1273Ser
Coding: c.3817G>T
MANE Select: NM_003458
Type: single nucleotide variant
Location: chr3:49653373 (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

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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
BSN p.His1842Arg 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-ala1273ser (accessed [today's date]).

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