Is BMP7 p.Ser248Leu (c.743C>T) pathogenic?

BMP7 p.Ser248Leu (c.743C>T) is classified Uncertain significance in BMP7 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-07-09). AlphaMissense: likely benign (0.1082); Ultra-rare (popmax 0.0733%, afr); Associated with BMP7-related disorder.

What condition is associated with BMP7 p.Ser248Leu (c.743C>T)?

BMP7 p.Ser248Leu (c.743C>T) is associated with BMP7-related disorder (ClinVar).

How common is BMP7 p.Ser248Leu (c.743C>T) in the general population?

BMP7 p.Ser248Leu (c.743C>T) is ultra-rare (popmax 0.0733%, afr) (gnomAD).

What do computational predictors say about BMP7 p.Ser248Leu (c.743C>T)?

AlphaMissense predicts likely benign (score 0.1082) — an in-silico prediction, not a clinical call.

BMP7 p.Ser248Leu

c.743C>T · rs145527493 · VCV2634610

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1082 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0733%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

BMP7-related disorder

Computational evidence

Protein change
AlphaMissense	0.1082	likely benign
REVEL	0.184	benign-leaning
SaProt	LLR -11.26	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.4	GERP -1.9, phastCons 1
Regional constraint	o/e 0.84	unconstrained · MANE · 93 kb · p 0.00035 · regional, not allelic
Overall
CADD	22.6	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 0.0733% African / African-American · 55/74,986 alleles

Filtering AF 0.0578% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0522%

Overall 0.00436% 70/1,606,648 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0733%	1,363
East Asian	0.00892%	11,213
European (non-Finnish)	0.000932%	107,257

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.Ser248Leu
Coding: c.743C>T
MANE Select: NM_001719
dbSNP: rs145527493
Type: single nucleotide variant
Location: chr20:57202492 (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

Disease context

BMP7-related disorder

Similar variants

BMP7 p.Leu160Phe Uncertain significance ★★ ⚠ same condition
BMP7 p.Ala329Gly Uncertain significance ★ ⚠ same condition
BMP7 p.Val415Ile Uncertain significance ★ ⚠ same condition
BMP7 p.Ala29Ser Uncertain significance ⚠ same condition
BMP7 p.Asn368= Likely benign same condition
BMP7 p.Gln49= Likely benign same condition
BMP7 p.Pro116= Likely benign same condition
BMP7 p.Thr294= Likely benign 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/bmp7-p-ser248leu (accessed [today's date]).

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