Is BMP8B p.Leu36Val (c.106C>G) pathogenic?

BMP8B p.Leu36Val (c.106C>G) is classified Uncertain significance in BMP8B (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-22). AlphaMissense: likely benign (0.1325); Ultra-rare (popmax 0.0879%, eas).

How common is BMP8B p.Leu36Val (c.106C>G) in the general population?

BMP8B p.Leu36Val (c.106C>G) is ultra-rare (popmax 0.0879%, eas) (gnomAD).

What do computational predictors say about BMP8B p.Leu36Val (c.106C>G)?

AlphaMissense predicts likely benign (score 0.1325) — an in-silico prediction, not a clinical call.

BMP8B p.Leu36Val

c.106C>G · rs929863491 · VCV3134577

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1325 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0879%, eas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1325	likely benign
REVEL	0.249	benign-leaning
SaProt	LLR -10.21	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.3	GERP 1.2, phastCons 1
Regional constraint	o/e 0.76	unconstrained · MANE · 173 bp · p 0.046 · regional, not allelic
Overall
CADD	21.4	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

Grpmax group 0.0879% East Asian · 17/19,342 alleles

Filtering AF 0.056% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0459%

Overall 0.00367% 41/1,117,776 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0879%	1,138
Remaining individualsnot grpmax-eligible	0.0586%	1,705
Middle Eastern	0.0384%	2,606
European (non-Finnish)	0.000109%	917,995

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: BMP8B
Protein: p.Leu36Val
Coding: c.106C>G
MANE Select: NM_001720
dbSNP: rs929863491
Type: single nucleotide variant
Location: chr1:39788380 (GRCh38)
Gene constraint: LOEUF 1.297 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.96

Full BMP8B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BMP8B c.1059+579A>G Benign/Likely benign ★★ same type
BMP8B p.Leu118= Likely benign ★★ same type
BMP8B p.Ser276Thr Benign ★★ same type
BMP8B p.Ser326= Benign/Likely benign ★★ same type
BMP8B c.673+3659A>G Conflicting classifications of pathogenicity ★ ⚠ same type
BMP8B p.Ala344Val Uncertain significance ★ ⚠ same type
BMP8B p.Ala348Thr Uncertain significance ★ ⚠ same type
BMP8B p.Ala361Thr 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/bmp8b-p-leu36val (accessed [today's date]).

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