Is BMP2 p.Ser37Ala (c.109T>G) pathogenic?

BMP2 p.Ser37Ala (c.109T>G) is classified Benign in BMP2 (ClinVar, Multiple submitters, 9 submitters; last evaluated 2026-02-02). AlphaMissense: likely benign (0.0611); Common (popmax 9.4%, eas) — too common for a highly-penetrant pathogenic allele; Associated with ventricular septal defect 1.

What condition is associated with BMP2 p.Ser37Ala (c.109T>G)?

BMP2 p.Ser37Ala (c.109T>G) is associated with ventricular septal defect 1 (ClinVar).

What do computational predictors say about BMP2 p.Ser37Ala (c.109T>G)?

AlphaMissense predicts likely benign (score 0.0611) — an in-silico prediction, not a clinical call.

BMP2 p.Ser37Ala

Q: How common is BMP2 p.Ser37Ala (c.109T>G) in the general population?

BMP2 p.Ser37Ala (c.109T>G) is common (popmax 9.4%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.109T>G · rs2273073 · VCV195137

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 9 submitters

AlphaMissense

likely benign

0.0611 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 9.4%, eas) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

ventricular septal defect 1

Computational evidence

Protein change
AlphaMissense	0.0611	likely benign
REVEL	0.086	moderately benign-leaning
SaProt	LLR -5.76	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 -0.015	GERP -3.4, phastCons 0.27
Regional constraint	o/e 0.92	unconstrained · MANE · 8,670 bp · p 0.13 · regional, not allelic
Overall
CADD	2.834	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 9.4% East Asian · 4,131/43,940 alleles

Filtering AF 9.16% ClinGen BA1/BS1 input FAF95, joint · FAF99 9.06%

Overall 2.06% 33,080/1,603,848 alleles · common exomes 30,610/1,451,642 · genomes 2,470/152,206 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	9.4%	11
South Asian	4.33%	23
Ashkenazi Jewishnot grpmax-eligible	3.15%	32
Remaining individualsnot grpmax-eligible	2.19%	46
European (non-Finnish)	1.82%	55
Middle Eastern	1.47%	68
Finnishnot grpmax-eligible	0.998%	100
Admixed American	0.829%	121
African / African-American	0.272%	368

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.Ser37Ala
Coding: c.109T>G
MANE Select: NM_001200
dbSNP: rs2273073
Type: single nucleotide variant
Location: chr20:6770235 (GRCh38)
Gene constraint: LOEUF 0.213 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 80.37 · 21 PDB
Residue 37: 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

ventricular septal defect 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

BMP2 p.Glu328Lys Pathogenic ⚠ same condition
BMP2 p.Arg154Ter Pathogenic/Likely pathogenic ★★ same type
BMP2 p.Arg170Ter Pathogenic/Likely pathogenic ★★ same type
BMP2 p.Cys329Ter Likely pathogenic ★★ same type
BMP2 p.Gln89Ter Pathogenic/Likely pathogenic ★★ same type
BMP2 p.Glu229Ter Pathogenic/Likely pathogenic ★★ same type
BMP2 p.Ser92Ter Pathogenic/Likely pathogenic ★★ same type
BMP2 p.Ala103Thr 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/bmp2-p-ser37ala (accessed [today's date]).

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