Is BMP2 p.Arg190Ser (c.570A>T) pathogenic?

BMP2 p.Arg190Ser (c.570A>T) is classified Benign in BMP2 (ClinVar, Multiple submitters, 8 submitters; last evaluated 2026-02-04). AlphaMissense: likely pathogenic (0.8094); Common (popmax 93.4%, afr) — too common for a highly-penetrant pathogenic allele; Associated with short stature, facial dysmorphism, and skeletal anomalies with or without cardiac anomalies.

What do computational predictors say about BMP2 p.Arg190Ser (c.570A>T)?

AlphaMissense predicts likely pathogenic (score 0.8094) — an in-silico prediction, not a clinical call.

BMP2 p.Arg190Ser

Q: What condition is associated with BMP2 p.Arg190Ser (c.570A>T)?

BMP2 p.Arg190Ser (c.570A>T) is associated with short stature, facial dysmorphism, and skeletal anomalies with or without cardiac anomalies (ClinVar).

Q: How common is BMP2 p.Arg190Ser (c.570A>T) in the general population?

BMP2 p.Arg190Ser (c.570A>T) is common (popmax 93.4%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.570A>T · rs235768 · VCV196322

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

AlphaMissense

likely pathogenic

0.8094 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 93.4%, afr) — too common for a highly-penetrant pathogenic allele

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

short stature, facial dysmorphism, and skeletal anomalies with or without cardiac anomalies

Computational evidence

Protein change
AlphaMissense	0.8094	likely pathogenic
REVEL	0.411	indeterminate
SaProt	LLR -10.59	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.7	GERP 2.8, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 8,670 bp · p 0.13 · regional, not allelic
Overall
CADD	23.7	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 93.4% African / African-American · 70,007/74,994 alleles

Filtering AF 92.8% ClinGen BA1/BS1 input FAF95, joint · FAF99 92.5%

Overall 64.3% 1,038,089/1,613,906 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	93.4%	1
East Asian	81.3%	1
Ashkenazi Jewishnot grpmax-eligible	81.2%	1
Middle Eastern	76.4%	1
Admixed American	70.4%	1
Remaining individualsnot grpmax-eligible	67.2%	1
Amishnot grpmax-eligible	63%	2
European (non-Finnish)	61.5%	2
South Asian	60.9%	2
Finnishnot grpmax-eligible	58%	2

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: BMP2
Protein: p.Arg190Ser
Coding: c.570A>T
MANE Select: NM_001200
dbSNP: rs235768
Type: single nucleotide variant
Location: chr20:6778468 (GRCh38)
Gene constraint: LOEUF 0.213 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 80.37 · 21 PDB
Residue 190: a UniProt-annotated variant site (in ssfsc1); a UniProt-annotated variant site (in)

Full BMP2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

short stature, facial dysmorphism, and skeletal anomalies with or without cardiac anomalies — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

BMP2 p.Arg154Ter Pathogenic/Likely pathogenic ★★ same condition
BMP2 p.Arg170Ter Pathogenic/Likely pathogenic ★★ same condition
BMP2 p.Cys329Ter Likely pathogenic ★★ same condition
BMP2 p.Ser87= Benign ★★ same condition
BMP2 p.Glu205Ter Pathogenic ★ same condition
BMP2 p.Glu27Ter Likely pathogenic ★ same condition
BMP2 p.Trp313Ter Likely pathogenic ★ same condition
BMP2 p.Val74fs Pathogenic ★ 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/bmp2-p-arg190ser (accessed [today's date]).

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