Is BMP8A p.Gln185= (c.555G>A) pathogenic?

BMP8A p.Gln185= (c.555G>A) is classified Likely benign in BMP8A (ClinVar, Single submitter, 1 submitter; last evaluated 2026-01-01). Very rare (popmax 0.00146%, nfe).

How common is BMP8A p.Gln185= (c.555G>A) in the general population?

BMP8A p.Gln185= (c.555G>A) is very rare (popmax 0.00146%, nfe) (gnomAD).

BMP8A p.Gln185=

c.555G>A · VCV4822231

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00146%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.99	acceptor loss · deltas
Constraint at this position
Conservation	phyloP 7.9	GERP 0.6, phastCons 1
Overall
CADD	13.52	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00146% European (non-Finnish) · 17/1,160,514 alleles

Filtering AF 0.000892% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000729%

Overall 0.00114% 18/1,585,458 alleles · very rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.0016%	62,314
European (non-Finnish)grpmax	0.00146%	68,265

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Gln185=
Coding: c.555G>A
MANE Select: NM_181809
Type: single nucleotide variant
Location: chr1:39511786 (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.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
BMP8A p.Ala374Thr 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-gln185 (accessed [today's date]).

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