Is BMP1 p.Pro104Ser (c.310C>T) pathogenic?

BMP1 p.Pro104Ser (c.310C>T) is classified Uncertain significance in BMP1 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-03-28). AlphaMissense: likely benign (0.0714); Ultra-rare (popmax 0.0666%, afr); Associated with Inborn genetic diseases.

What condition is associated with BMP1 p.Pro104Ser (c.310C>T)?

BMP1 p.Pro104Ser (c.310C>T) is associated with Inborn genetic diseases (ClinVar).

How common is BMP1 p.Pro104Ser (c.310C>T) in the general population?

BMP1 p.Pro104Ser (c.310C>T) is ultra-rare (popmax 0.0666%, afr) (gnomAD).

What do computational predictors say about BMP1 p.Pro104Ser (c.310C>T)?

AlphaMissense predicts likely benign (score 0.0714) — an in-silico prediction, not a clinical call.

BMP1 p.Pro104Ser

c.310C>T · rs147403315 · VCV1327763

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.0714 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0666%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0714	likely benign
REVEL	0.029	moderately benign-leaning
SaProt	LLR -6.41	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 1.1	GERP -3.3, phastCons 0.54
Regional constraint	o/e 1.16	unconstrained · MANE · 11 kb · p 0.038 · regional, not allelic
Overall
CADD	9.012	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 0.0666% African / African-American · 50/75,054 alleles

Filtering AF 0.0519% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0466%

Overall 0.0044% 71/1,614,136 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0666%	1,501
Middle Eastern	0.0165%	6,062
Admixed American	0.0133%	7,503
Remaining individualsnot grpmax-eligible	0.0032%	31,252
European (non-Finnish)	0.000847%	118,002

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: BMP1
Protein: p.Pro104Ser
Coding: c.310C>T
MANE Select: NM_006129
dbSNP: rs147403315
Type: single nucleotide variant
Location: chr8:22176190 (GRCh38)
Gene constraint: LOEUF 0.648 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.89 · 8 PDB
Residue 104: the 'disordered' region

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.Pro104Arg Uncertain significance ★ ⚠ same residue
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

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-pro104ser (accessed [today's date]).

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