Is BMP8A p.Val109= (c.327C>T) pathogenic?

BMP8A p.Val109= (c.327C>T) is classified Likely benign in BMP8A (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-01). Ultra-rare (popmax 0.0239%, amr).

How common is BMP8A p.Val109= (c.327C>T) in the general population?

BMP8A p.Val109= (c.327C>T) is ultra-rare (popmax 0.0239%, amr) (gnomAD).

BMP8A p.Val109=

c.327C>T · rs4012665 · VCV2638714

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0239%, amr)

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 0.069	GERP -2.1, phastCons 0.92
Overall
CADD	12.02	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0239% Admixed American · 13/54,302 alleles

Filtering AF 0.0141% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0111%

Overall 0.00648% 101/1,559,646 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0239%	4,177
Remaining individualsnot grpmax-eligible	0.0149%	6,708
European (non-Finnish)	0.0067%	14,929
African / African-American	0.00143%	69,902

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: BMP8A
Protein: p.Val109=
Coding: c.327C>T
MANE Select: NM_181809
dbSNP: rs4012665
Type: single nucleotide variant
Location: chr1:39492318 (GRCh38)
Gene constraint: LOEUF 1.337 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.87

Full BMP8A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BMP8A p.Val109Ile Uncertain significance ★ ⚠ same residue
BMP8A p.Ala144Val Uncertain significance ★★ ⚠ same type
BMP8A p.Arg293His Benign ★★ same type
BMP8A p.Ala102Thr Uncertain significance ★ ⚠ same type
BMP8A p.Ala201Thr Uncertain significance ★ ⚠ same type
BMP8A p.Ala264Thr Uncertain significance ★ ⚠ same type
BMP8A p.Ala348Val Uncertain significance ★ ⚠ same type
BMP8A p.Ala365Val 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/bmp8a-p-val109 (accessed [today's date]).

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