Is BMS1 p.Ala549Thr (c.1645G>A) pathogenic?

BMS1 p.Ala549Thr (c.1645G>A) is classified Benign in BMS1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2020-08-21). AlphaMissense: likely benign (0.0669); Rare (popmax 0.408%, eas); Associated with BMS1-related disorder.

What condition is associated with BMS1 p.Ala549Thr (c.1645G>A)?

BMS1 p.Ala549Thr (c.1645G>A) is associated with BMS1-related disorder (ClinVar).

How common is BMS1 p.Ala549Thr (c.1645G>A) in the general population?

BMS1 p.Ala549Thr (c.1645G>A) is rare (popmax 0.408%, eas) (gnomAD).

What do computational predictors say about BMS1 p.Ala549Thr (c.1645G>A)?

AlphaMissense predicts likely benign (score 0.0669) — an in-silico prediction, not a clinical call.

BMS1 p.Ala549Thr

c.1645G>A · rs139656912 · VCV3036677

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0669 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.408%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

BMS1-related disorder

Computational evidence

Protein change
AlphaMissense	0.0669	likely benign
REVEL	0.011	strongly benign-leaning
SaProt	LLR -6.69	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.4	GERP -2.5
Regional constraint	o/e 1.02	unconstrained · MANE · 26 kb · p 0.68 · regional, not allelic
Overall
CADD	0.106	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 0.408% East Asian · 183/44,876 alleles

Filtering AF 0.359% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.341%

Overall 0.0141% 228/1,614,218 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.408%	245
Remaining individualsnot grpmax-eligible	0.0592%	1,689
Middle Eastern	0.0165%	6,060
Admixed American	0.00333%	30,014
South Asian	0.0022%	45,543
European (non-Finnish)	0.000254%	393,348

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.Ala549Thr
Coding: c.1645G>A
MANE Select: NM_014753
dbSNP: rs139656912
Type: single nucleotide variant
Location: chr10:42796889 (GRCh38)
Gene constraint: LOEUF 0.507 · pLI 0.50 (gnomAD)
Structure: AlphaFold pLDDT 72.04 · 3 PDB
Residue 549: the 'disordered' region

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

Disease context

BMS1-related disorder

Similar variants

BMS1 c.779+7T>A Likely benign same condition
BMS1 c.779+8A>G Likely benign same condition
BMS1 p.Ala864Thr Benign ⚠ same condition
BMS1 p.Asp505= Likely benign same condition
BMS1 p.Gln419Glu Benign same condition
BMS1 p.Lys399= Benign same condition
BMS1 p.Phe1047Leu Benign same condition
BMS1 p.Thr583= Benign same condition

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-ala549thr (accessed [today's date]).

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