Is BMP5 p.Asn282= (c.846C>T) pathogenic?

BMP5 p.Asn282= (c.846C>T) is classified Benign in BMP5 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-11-18). Common (popmax 14.5%, eas) — too common for a highly-penetrant pathogenic allele; Associated with BMP5-related disorder.

What condition is associated with BMP5 p.Asn282= (c.846C>T)?

BMP5 p.Asn282= (c.846C>T) is associated with BMP5-related disorder (ClinVar).

BMP5 p.Asn282=

Q: How common is BMP5 p.Asn282= (c.846C>T) in the general population?

BMP5 p.Asn282= (c.846C>T) is common (popmax 14.5%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.846C>T · rs41271330 · VCV3060109

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Common

common (popmax 14.5%, eas) — too common for a highly-penetrant pathogenic allele

Conditions

BMP5-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -3.3	GERP -2.4
Overall
CADD	0.381	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 14.5% East Asian · 6,507/44,832 alleles

Filtering AF 14.2% ClinGen BA1/BS1 input FAF95, joint · FAF99 14.1%

Overall 12.1% 194,521/1,612,094 alleles · common

Ancestry group	Frequency	1 in
East Asiangrpmax	14.5%	7
European (non-Finnish)	13.1%	8
Finnishnot grpmax-eligible	12.5%	8
Remaining individualsnot grpmax-eligible	11.9%	8
Admixed American	11.8%	8
Ashkenazi Jewishnot grpmax-eligible	10.8%	9
Amishnot grpmax-eligible	8.99%	11
South Asian	5.77%	17
Middle Eastern	3.14%	32
African / African-American	2.54%	39

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.Asn282=
Coding: c.846C>T
MANE Select: NM_021073
dbSNP: rs41271330
Type: single nucleotide variant
Location: chr6:55774230 (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

Disease context

BMP5-related disorder

Similar variants

BMP5 p.Ser347Arg Uncertain significance ★ ⚠ same condition
BMP5 p.Gln298= Likely benign same condition
BMP5 p.Ile127Lys Benign same condition
BMP5 p.Ser37= Benign same condition
BMP5 p.Tyr377= Benign same condition
BMP5 p.Val101= Likely benign same condition
BMP5 c.1105-29GT[11] Likely benign same condition
BMP5 c.1105-29GT[15] 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/bmp5-p-asn282 (accessed [today's date]).

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