Is BMP8A p.Arg46His (c.137G>A) pathogenic?

BMP8A p.Arg46His (c.137G>A) is classified Uncertain significance in BMP8A (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-03). AlphaMissense: likely benign (0.1979); Absent from gnomAD v4.1.

How common is BMP8A p.Arg46His (c.137G>A) in the general population?

BMP8A p.Arg46His (c.137G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BMP8A p.Arg46His (c.137G>A)?

AlphaMissense predicts likely benign (score 0.1979) — an in-silico prediction, not a clinical call.

BMP8A p.Arg46His

c.137G>A · VCV3481190

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1979 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,233,756)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1979	likely benign
REVEL	0.295	indeterminate
SaProt	LLR -10.93	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.9	GERP -0.85, phastCons 1
Regional constraint	o/e 0.76	unconstrained · MANE · 167 bp · p 0.035 · regional, not allelic
Overall
CADD	26.1	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

No allele count reported in gnomAD v4.1 (AN 1,233,756). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: BMP8A
Protein: p.Arg46His
Coding: c.137G>A
MANE Select: NM_181809
Type: single nucleotide variant
Location: chr1:39492128 (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-arg46his (accessed [today's date]).

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