Is BMP1 p.Thr325Ser (c.974C>G) pathogenic?

BMP1 p.Thr325Ser (c.974C>G) is classified Uncertain significance in BMP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-26). AlphaMissense: likely benign (0.2234); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with BMP1 p.Thr325Ser (c.974C>G)?

BMP1 p.Thr325Ser (c.974C>G) is associated with Inborn genetic diseases (ClinVar).

How common is BMP1 p.Thr325Ser (c.974C>G) in the general population?

BMP1 p.Thr325Ser (c.974C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BMP1 p.Thr325Ser (c.974C>G)?

AlphaMissense predicts likely benign (score 0.2234) — an in-silico prediction, not a clinical call.

BMP1 p.Thr325Ser

c.974C>G · VCV3261165

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2234 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2234	likely benign
REVEL	0.085	moderately benign-leaning
SaProt	LLR -11.41	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.9, phastCons 1
Regional constraint	o/e 0.84	unconstrained · MANE · 35 kb · p 1e-07 · regional, not allelic
Overall
CADD	23.5	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: BMP1
Protein: p.Thr325Ser
Coding: c.974C>G
MANE Select: NM_006129
Type: single nucleotide variant
Location: chr8:22180380 (GRCh38)
Gene constraint: LOEUF 0.648 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.89 · 8 PDB
Residue 325: a disulfide bond; the cub 1 domain

Full BMP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

BMP1 p.Ala657Thr Uncertain significance ★★ ⚠ same condition
BMP1 p.Arg351His Uncertain significance ★★ ⚠ same condition
BMP1 p.Arg351Pro Uncertain significance ★★ ⚠ same condition
BMP1 p.Arg395His Uncertain significance ★★ ⚠ same condition
BMP1 p.Arg508His Uncertain significance ★★ ⚠ same condition
BMP1 p.Arg524Cys Uncertain significance ★★ ⚠ same condition
BMP1 p.Arg562Trp Uncertain significance ★★ ⚠ same condition
BMP1 p.Arg628Cys Uncertain significance ★★ ⚠ 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/bmp1-p-thr325ser (accessed [today's date]).

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