Is BMP7 p.Asp85Glu (c.255C>A) pathogenic?

BMP7 p.Asp85Glu (c.255C>A) is classified Uncertain significance in BMP7 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-03-04). AlphaMissense: likely pathogenic (0.8369); Ultra-rare (popmax 0.0496%, mid).

How common is BMP7 p.Asp85Glu (c.255C>A) in the general population?

BMP7 p.Asp85Glu (c.255C>A) is ultra-rare (popmax 0.0496%, mid) (gnomAD).

What do computational predictors say about BMP7 p.Asp85Glu (c.255C>A)?

AlphaMissense predicts likely pathogenic (score 0.8369) — an in-silico prediction, not a clinical call.

BMP7 p.Asp85Glu

c.255C>A · rs777610187 · VCV2166989

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8369 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0496%, mid)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.8369	likely pathogenic
REVEL	0.574	indeterminate
SaProt	LLR -9.00	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 7.2	GERP 0.85, phastCons 1
Regional constraint	o/e 0.84	unconstrained · MANE · 93 kb · p 0.00035 · regional, not allelic
Overall
CADD	26.7	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 0.0496% Middle Eastern · 3/6,052 alleles

Filtering AF 0.0134% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00719%

Overall 0.00158% 23/1,453,448 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0496%	2,017
Admixed American	0.0102%	9,817
Remaining individualsnot grpmax-eligible	0.00644%	15,535
European (non-Finnish)	0.00085%	117,649

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.Asp85Glu
Coding: c.255C>A
MANE Select: NM_001719
dbSNP: rs777610187
Type: single nucleotide variant
Location: chr20:57265868 (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.Asp85Val Pathogenic same residue
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

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-asp85glu (accessed [today's date]).

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