Is BMPR1A p.Cys82Phe (c.245G>T) pathogenic?

BMPR1A p.Cys82Phe (c.245G>T) is classified Likely pathogenic in BMPR1A (ClinVar, Single submitter, 1 submitter; last evaluated 2016-09-19). AlphaMissense: likely pathogenic (0.9979); Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with BMPR1A p.Cys82Phe (c.245G>T)?

BMPR1A p.Cys82Phe (c.245G>T) is associated with hereditary neoplastic syndrome (ClinVar).

How common is BMPR1A p.Cys82Phe (c.245G>T) in the general population?

BMPR1A p.Cys82Phe (c.245G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BMPR1A p.Cys82Phe (c.245G>T)?

AlphaMissense predicts likely pathogenic (score 0.9979) — an in-silico prediction, not a clinical call.

BMPR1A p.Cys82Phe

c.245G>T · rs1554888310 · VCV486819

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9979 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.9979	likely pathogenic ✓ concordant with ClinVar · top 9% in BMPR1A
REVEL	0.961	strongly pathogenic-leaning
SaProt	LLR -16.02	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.9, phastCons 1
Regional constraint	o/e 0.28	constrained · MANE · 2,017 bp · p 8.9e-07 · regional, not allelic
Overall
CADD	33.0	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: BMPR1A
Protein: p.Cys82Phe
Coding: c.245G>T
MANE Select: NM_004329
dbSNP: rs1554888310
Type: single nucleotide variant
Location: chr10:86892141 (GRCh38)
Gene constraint: LOEUF 0.195 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 82.86 · 11 PDB
Residue 82: a disulfide bond; a UniProt-annotated variant site (in jps); a β-strand

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.Cys82= Benign/Likely benign ★★ same residue
BMPR1A p.Cys82Ter Pathogenic ★ same residue
BMPR1A p.Cys82Tyr Conflicting classifications of pathogenicity ★ ⚠ same residue
BMPR1A p.Cys82Gly Uncertain significance ★ ⚠ same residue
BMPR1A p.Cys82Ser Uncertain significance ★ ⚠ same residue
BMPR1A p.Cys82Trp Uncertain significance ★ ⚠ same residue
BMPR1A c.1166+1G>A Likely pathogenic ★★ same condition
BMPR1A c.1473+1G>A Pathogenic/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-cys82phe (accessed [today's date]).

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