Is BMP1 p.Val734Ile (c.2200G>A) pathogenic?

BMP1 p.Val734Ile (c.2200G>A) is classified Uncertain significance in BMP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-09-10). AlphaMissense: likely benign (0.0746); Very rare (popmax 0.00441%, nfe).

How common is BMP1 p.Val734Ile (c.2200G>A) in the general population?

BMP1 p.Val734Ile (c.2200G>A) is very rare (popmax 0.00441%, nfe) (gnomAD).

What do computational predictors say about BMP1 p.Val734Ile (c.2200G>A)?

AlphaMissense predicts likely benign (score 0.0746) — an in-silico prediction, not a clinical call.

BMP1 p.Val734Ile

c.2200G>A · rs148552467 · VCV1491513

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0746 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00441%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0746	likely benign
REVEL	0.284	benign-leaning
SaProt	LLR -4.52	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 2.9	GERP -2.3, phastCons 1
Regional constraint	o/e 0.84	unconstrained · MANE · 35 kb · p 1e-07 · regional, not allelic
Overall
CADD	20.9	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 0.00441% European (non-Finnish) · 52/1,179,924 alleles

Filtering AF 0.00342% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0031%

Overall 0.00359% 58/1,613,620 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00441%	22,691
Admixed American	0.00334%	29,982
Remaining individualsnot grpmax-eligible	0.0032%	31,234
African / African-American	0.00267%	37,468

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.Val734Ile
Coding: c.2200G>A
MANE Select: NM_006129
dbSNP: rs148552467
Type: single nucleotide variant
Location: chr8:22201895 (GRCh38)
Gene constraint: LOEUF 0.648 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.89 · 8 PDB
Residue 734: a disulfide bond; the egf-like 2; calcium-binding domain

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

Similar variants

BMP1 p.Cys183Ter Pathogenic/Likely pathogenic ★★ same type
BMP1 p.Gln70Ter Pathogenic/Likely pathogenic ★★ same type
BMP1 c.1443+6T>C Uncertain significance ★★ same type
BMP1 c.1639+4C>G Uncertain significance ★★ same type
BMP1 c.2233+4C>T Uncertain significance ★★ same type
BMP1 c.*452A>C Uncertain significance ★★ same type
BMP1 p.Ala538Val Uncertain significance ★★ ⚠ same type
BMP1 p.Ala657Thr 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/bmp1-p-val734ile (accessed [today's date]).

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