Is BMP7 p.Ala364Ser (c.1090G>T) pathogenic?

BMP7 p.Ala364Ser (c.1090G>T) is classified Uncertain significance in BMP7 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-05). AlphaMissense: likely benign (0.0795); Ultra-rare (popmax 0.0417%, sas).

How common is BMP7 p.Ala364Ser (c.1090G>T) in the general population?

BMP7 p.Ala364Ser (c.1090G>T) is ultra-rare (popmax 0.0417%, sas) (gnomAD).

What do computational predictors say about BMP7 p.Ala364Ser (c.1090G>T)?

AlphaMissense predicts likely benign (score 0.0795) — an in-silico prediction, not a clinical call.

BMP7 p.Ala364Ser

c.1090G>T · rs748347077 · VCV2066422

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0795 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0417%, sas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0795	likely benign
REVEL	0.789	moderately pathogenic-leaning
SaProt	LLR -5.20	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.8	GERP -4.7, phastCons 1
Regional constraint	o/e 0.50	unconstrained · MANE · 2,345 bp · p 4.2e-08 · regional, not allelic
Overall
CADD	19.22	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 0.0417% South Asian · 38/91,094 alleles

Filtering AF 0.0312% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0275%

Overall 0.00248% 40/1,614,084 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0417%	2,397
Remaining individualsnot grpmax-eligible	0.0032%	31,245

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: BMP7
Protein: p.Ala364Ser
Coding: c.1090G>T
MANE Select: NM_001719
dbSNP: rs748347077
Type: single nucleotide variant
Location: chr20:57173256 (GRCh38)
Gene constraint: LOEUF 0.523 · pLI 0.96 (gnomAD)
Structure: AlphaFold pLDDT 76.50 · 4 PDB
Residue 364: a disulfide bond

Full BMP7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BMP7 p.Arg150His Uncertain significance ★★ ⚠ same type
BMP7 p.Arg267Gln Uncertain significance ★★ ⚠ same type
BMP7 p.His241Tyr Uncertain significance ★★ ⚠ same type
BMP7 p.Ile386Val Uncertain significance ★★ ⚠ same type
BMP7 p.Leu160Phe Uncertain significance ★★ same type
BMP7 p.Pro116Ser Uncertain significance ★★ ⚠ same type
BMP7 p.Ser248Leu Uncertain significance ★★ ⚠ same type
BMP7 p.Thr251Met 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/bmp7-p-ala364ser (accessed [today's date]).

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