Is BMPR1A p.Pro68Thr (c.202C>A) pathogenic?

BMPR1A p.Pro68Thr (c.202C>A) is classified Uncertain significance in BMPR1A (ClinVar, Single submitter, 1 submitter; last evaluated 2018-06-29). AlphaMissense: ambiguous (0.5443); Very rare (popmax 6.84e-05%); Associated with hereditary neoplastic syndrome.

What condition is associated with BMPR1A p.Pro68Thr (c.202C>A)?

BMPR1A p.Pro68Thr (c.202C>A) is associated with hereditary neoplastic syndrome (ClinVar).

How common is BMPR1A p.Pro68Thr (c.202C>A) in the general population?

BMPR1A p.Pro68Thr (c.202C>A) is very rare (popmax 6.84e-05%) (gnomAD).

What do computational predictors say about BMPR1A p.Pro68Thr (c.202C>A)?

AlphaMissense predicts ambiguous (score 0.5443) — an in-silico prediction, not a clinical call.

BMPR1A p.Pro68Thr

c.202C>A · rs1589763452 · VCV820556

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5443 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 6.84e-05%)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.5443	ambiguous
REVEL	0.697	pathogenic-leaning
SaProt	LLR -3.47	tolerated
⇒ REVEL calls this damaging; SaProt does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.7, phastCons 1
Regional constraint	o/e 0.82	unconstrained · MANE · 14 kb · p 0.1 · regional, not allelic
Overall
CADD	26.3	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 6.84e-05%

Overall 6.84e-05% 1/1,461,832 alleles · very rare

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.Pro68Thr
Coding: c.202C>A
MANE Select: NM_004329
dbSNP: rs1589763452
Type: single nucleotide variant
Location: chr10:86890196 (GRCh38)
Gene constraint: LOEUF 0.195 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 82.86 · 11 PDB
Residue 68: a disulfide bond

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

Disease context

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

Similar variants

BMPR1A p.Pro68Ala Uncertain significance ★★ ⚠ same residue
BMPR1A p.Pro68= Benign/Likely benign ★★ same residue
BMPR1A p.Pro68Ser Uncertain significance ★ ⚠ same residue
BMPR1A c.1166+1G>A 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-pro68thr (accessed [today's date]).

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