Is BMP5 p.Ala118Asp (c.353C>A) pathogenic?

BMP5 p.Ala118Asp (c.353C>A) is classified Uncertain significance in BMP5 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-03). AlphaMissense: likely benign (0.1374); Very rare (popmax 0.00267%, afr).

How common is BMP5 p.Ala118Asp (c.353C>A) in the general population?

BMP5 p.Ala118Asp (c.353C>A) is very rare (popmax 0.00267%, afr) (gnomAD).

What do computational predictors say about BMP5 p.Ala118Asp (c.353C>A)?

AlphaMissense predicts likely benign (score 0.1374) — an in-silico prediction, not a clinical call.

BMP5 p.Ala118Asp

c.353C>A · rs778186001 · VCV2315691

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1374 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1374	likely benign
REVEL	0.2	benign-leaning
SaProt	LLR -6.94	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 12	GERP 2.5, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 119 kb · p 0.39 · regional, not allelic
Overall
CADD	22.3	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00267% African / African-American · 2/74,814 alleles

Filtering AF 0.000444% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.000186% 3/1,613,288 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00267%	37,407
South Asian	0.0011%	91,068

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: BMP5
Protein: p.Ala118Asp
Coding: c.353C>A
MANE Select: NM_021073
dbSNP: rs778186001
Type: single nucleotide variant
Location: chr6:55874513 (GRCh38)
Gene constraint: LOEUF 0.711 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.85

Full BMP5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BMP5 p.Ala103Thr Uncertain significance ★ ⚠ same type
BMP5 p.Ala25Thr Uncertain significance ★ ⚠ same type
BMP5 p.Ala307Glu Uncertain significance ★ ⚠ same type
BMP5 p.Ala317Val Uncertain significance ★ ⚠ same type
BMP5 p.Ala74Thr Uncertain significance ★ ⚠ same type
BMP5 p.Ala77Val Uncertain significance ★ ⚠ same type
BMP5 p.Arg125Cys Uncertain significance ★ ⚠ same type
BMP5 p.Arg125His 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/bmp5-p-ala118asp (accessed [today's date]).

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