Is BMS1 p.Asp148Tyr (c.442G>T) pathogenic?

BMS1 p.Asp148Tyr (c.442G>T) is classified Uncertain significance in BMS1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-29). AlphaMissense: likely pathogenic (0.9695); Very rare (popmax 0.00427%, nfe).

How common is BMS1 p.Asp148Tyr (c.442G>T) in the general population?

BMS1 p.Asp148Tyr (c.442G>T) is very rare (popmax 0.00427%, nfe) (gnomAD).

What do computational predictors say about BMS1 p.Asp148Tyr (c.442G>T)?

AlphaMissense predicts likely pathogenic (score 0.9695) — an in-silico prediction, not a clinical call.

BMS1 p.Asp148Tyr

c.442G>T · VCV3992263

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9695 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00427%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9695	likely pathogenic · top 9% in BMS1
REVEL	0.695	pathogenic-leaning
SaProt	LLR -17.14	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.5, phastCons 1
Regional constraint	o/e 0.77	unconstrained · MANE · 7,350 bp · p 3.4e-05 · regional, not allelic
Overall
CADD	33.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.00427% European (non-Finnish) · 37/866,158 alleles

Filtering AF 0.00315% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00275%

Overall 0.00305% 38/1,245,356 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00427%	23,410
African / African-American	0.00147%	67,898

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: BMS1
Protein: p.Asp148Tyr
Coding: c.442G>T
MANE Select: NM_014753
Type: single nucleotide variant
Location: chr10:42787242 (GRCh38)
Gene constraint: LOEUF 0.507 · pLI 0.50 (gnomAD)
Structure: AlphaFold pLDDT 72.04 · 3 PDB
Residue 148: the bms1-type g domain; a β-strand

Full BMS1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BMS1 p.Asp148His Uncertain significance ★ ⚠ same residue
BMS1 p.Ala214Val Benign/Likely benign ★★ same type
BMS1 p.Ala500= Benign/Likely benign ★★ same type
BMS1 p.Arg237His Benign ★★ same type
BMS1 p.Arg38Trp Benign/Likely benign ★★ ⚠ same type
BMS1 p.Arg863= Benign ★★ same type
BMS1 p.Asp768Asn Benign ★★ same type
BMS1 p.Glu1278= Likely benign ★★ 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/bms1-p-asp148tyr (accessed [today's date]).

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