Is BMPR1A p.His178= (c.534T>C) pathogenic?

BMPR1A p.His178= (c.534T>C) is classified Likely benign in BMPR1A (ClinVar, Single submitter, 1 submitter; last evaluated 2026-05-24). Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with BMPR1A p.His178= (c.534T>C)?

BMPR1A p.His178= (c.534T>C) is associated with hereditary neoplastic syndrome (ClinVar).

How common is BMPR1A p.His178= (c.534T>C) in the general population?

BMPR1A p.His178= (c.534T>C) is absent from gnomAD v4.1 (gnomAD).

BMPR1A p.His178=

c.534T>C · VCV4867566

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>G here scores Δ0.81 · evaluated, not missing
Constraint at this position
Conservation	phyloP 0.13	GERP -4.9, phastCons 0.99
Overall
CADD	6.145	PHRED · no single calibrated threshold — expert panels disagree

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.His178=
Coding: c.534T>C
MANE Select: NM_004329
Type: single nucleotide variant
Location: chr10:86912243 (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

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

Similar variants

BMPR1A p.His178Arg Uncertain significance ★★ ⚠ same residue
BMPR1A p.His178Gln Uncertain significance ★★ ⚠ same residue
BMPR1A p.His178Tyr 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-his178 (accessed [today's date]).

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