Is BMPR1A p.Leu26Val (c.76C>G) pathogenic?

BMPR1A p.Leu26Val (c.76C>G) is classified Uncertain significance in BMPR1A (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-30). AlphaMissense: likely benign (0.0813); Very rare (popmax 8.47e-05%, nfe); Associated with juvenile polyposis syndrome.

What condition is associated with BMPR1A p.Leu26Val (c.76C>G)?

BMPR1A p.Leu26Val (c.76C>G) is associated with juvenile polyposis syndrome (ClinVar).

How common is BMPR1A p.Leu26Val (c.76C>G) in the general population?

BMPR1A p.Leu26Val (c.76C>G) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

How is Juvenile polyposis syndrome inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about BMPR1A p.Leu26Val (c.76C>G)?

AlphaMissense predicts likely benign (score 0.0813) — an in-silico prediction, not a clinical call.

BMPR1A p.Leu26Val

c.76C>G · rs2539429870 · VCV2824907

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0813 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

juvenile polyposis syndrome

Computational evidence

Protein change
AlphaMissense	0.0813	likely benign
REVEL	0.253	benign-leaning
SaProt	LLR -6.50	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.8	GERP 2.6, phastCons 1
Regional constraint	o/e 0.82	unconstrained · MANE · 14 kb · p 0.1 · regional, not allelic
Overall
CADD	21.4	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,179,960 alleles

Overall 6.2e-05% 1/1,612,894 alleles · very rare exomes 1/1,460,598 · genomes 0/152,296 · joint denominator

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: BMPR1A
Protein: p.Leu26Val
Coding: c.76C>G
MANE Select: NM_004329
dbSNP: rs2539429870
Type: single nucleotide variant
Location: chr10:86890070 (GRCh38)
Gene constraint: LOEUF 0.195 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 82.86 · 11 PDB

Full BMPR1A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

juvenile polyposis syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Juvenile polyposis syndrome (Orphanet):

Inheritance: Autosomal dominant
Onset: Adolescent, Adult, Childhood, Infancy
Prevalence: 1-9 / 100 000 (Europe)

Similar variants

BMPR1A p.Leu26= Benign/Likely benign ★★ same residue
BMPR1A p.Leu26Pro Uncertain significance ★ ⚠ same residue
BMPR1A c.1166+1G>A Likely pathogenic ★★ same condition
BMPR1A c.1343-2A>G Likely pathogenic ★★ same condition
BMPR1A c.1473+1G>A Pathogenic/Likely pathogenic ★★ same condition
BMPR1A c.1473+1G>C Pathogenic/Likely pathogenic ★★ same condition
BMPR1A c.230+1G>A Likely pathogenic ★★ same condition
BMPR1A c.333+1G>A Likely pathogenic ★★ 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/bmpr1a-p-leu26val (accessed [today's date]).

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