Is BMP7 p.Ser40Arg (c.120C>G) pathogenic?

BMP7 p.Ser40Arg (c.120C>G) is classified Uncertain significance in BMP7 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-14). AlphaMissense: likely pathogenic (0.9226); Very rare (popmax 0.00684%, afr).

How common is BMP7 p.Ser40Arg (c.120C>G) in the general population?

BMP7 p.Ser40Arg (c.120C>G) is very rare (popmax 0.00684%, afr) (gnomAD).

What do computational predictors say about BMP7 p.Ser40Arg (c.120C>G)?

AlphaMissense predicts likely pathogenic (score 0.9226) — an in-silico prediction, not a clinical call.

BMP7 p.Ser40Arg

c.120C>G · VCV4214321

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9226 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00684%, afr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9226	likely pathogenic
REVEL	0.431	indeterminate
SaProt	LLR -7.18	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.7	GERP -3.3, phastCons 1
Regional constraint	o/e 0.84	unconstrained · MANE · 93 kb · p 0.00035 · regional, not allelic
Overall
CADD	23.9	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 0.00684% African / African-American · 5/73,064 alleles

Filtering AF 0.0026% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00165%

Overall 0.000323% 5/1,549,488 alleles · very rare

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.Ser40Arg
Coding: c.120C>G
MANE Select: NM_001719
Type: single nucleotide variant
Location: chr20:57266003 (GRCh38)
Gene constraint: LOEUF 0.523 · pLI 0.96 (gnomAD)
Structure: AlphaFold pLDDT 76.50 · 4 PDB

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-ser40arg (accessed [today's date]).

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