Is BMP7 p.Asn321Ser (c.962A>G) pathogenic?

BMP7 p.Asn321Ser (c.962A>G) is classified Benign in BMP7 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-07-24). AlphaMissense: likely benign (0.0868); Low-frequency (popmax 2.06%, mid); Associated with congenital total pulmonary venous return anomaly.

What condition is associated with BMP7 p.Asn321Ser (c.962A>G)?

BMP7 p.Asn321Ser (c.962A>G) is associated with congenital total pulmonary venous return anomaly (ClinVar).

How common is BMP7 p.Asn321Ser (c.962A>G) in the general population?

BMP7 p.Asn321Ser (c.962A>G) is low-frequency (popmax 2.06%, mid) (gnomAD).

What do computational predictors say about BMP7 p.Asn321Ser (c.962A>G)?

AlphaMissense predicts likely benign (score 0.0868) — an in-silico prediction, not a clinical call.

BMP7 p.Asn321Ser

c.962A>G · rs61733438 · VCV771049

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.0868 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 2.06%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

congenital total pulmonary venous return anomaly

Computational evidence

Protein change
AlphaMissense	0.0868	likely benign
REVEL	0.176	moderately benign-leaning
SaProt	LLR -5.12	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 4.2	GERP 0.56, phastCons 1
Regional constraint	o/e 0.84	unconstrained · MANE · 93 kb · p 0.00035 · regional, not allelic
Overall
CADD	12.09	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 2.06% Middle Eastern · 125/6,062 alleles

Filtering AF 1.77% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.7%

Overall 0.363% 5,853/1,610,820 alleles · low-frequency

Ancestry group	Frequency	1 in
Middle Easterngrpmax	2.06%	48
South Asian	1.81%	55
Ashkenazi Jewishnot grpmax-eligible	1.57%	64
Admixed American	0.572%	175
Remaining individualsnot grpmax-eligible	0.519%	193
European (non-Finnish)	0.243%	411
African / African-American	0.0933%	1,072
Finnishnot grpmax-eligible	0.0212%	4,718
East Asian	0.00669%	14,952

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.Asn321Ser
Coding: c.962A>G
MANE Select: NM_001719
dbSNP: rs61733438
Type: single nucleotide variant
Location: chr20:57175004 (GRCh38)
Gene constraint: LOEUF 0.523 · pLI 0.96 (gnomAD)
Structure: AlphaFold pLDDT 76.50 · 4 PDB
Residue 321: a UniProt-annotated variant site (in)

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

Disease context

congenital total pulmonary venous return anomaly — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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-asn321ser (accessed [today's date]).

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