Is JPH2 p.Thr287= (c.861C>T) pathogenic?

JPH2 p.Thr287= (c.861C>T) is classified Likely benign in JPH2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-09-02). Ultra-rare (popmax 0.0213%, afr); Associated with hypertrophic cardiomyopathy.

What condition is associated with JPH2 p.Thr287= (c.861C>T)?

JPH2 p.Thr287= (c.861C>T) is associated with hypertrophic cardiomyopathy (ClinVar).

How common is JPH2 p.Thr287= (c.861C>T) in the general population?

JPH2 p.Thr287= (c.861C>T) is ultra-rare (popmax 0.0213%, afr) (gnomAD).

JPH2 p.Thr287=

c.861C>T · rs565508885 · VCV1092695

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0213%, afr)

Conditions

hypertrophic cardiomyopathy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.5	GERP -0.48, phastCons 1
Overall
CADD	8.716	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0213% African / African-American · 16/75,004 alleles

Filtering AF 0.0133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0109%

Overall 0.00112% 18/1,611,200 alleles · ultra-rare exomes 8/1,458,974 · genomes 10/152,226 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0213%	4,688
Remaining individualsnot grpmax-eligible	0.0016%	62,450
South Asian	0.00111%	90,474

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: JPH2
Protein: p.Thr287=
Coding: c.861C>T
MANE Select: NM_020433
dbSNP: rs565508885
Type: single nucleotide variant
Location: chr20:44159926 (GRCh38)
Gene constraint: LOEUF 1.051 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 65.09 · 2 PDB

Full JPH2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

hypertrophic cardiomyopathy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

JPH2 p.Thr287Ala Uncertain significance ★ ⚠ same residue
JPH2 p.Thr161Lys Pathogenic/Likely pathogenic ★★ same condition
JPH2 p.Ala181Thr Uncertain significance ★★ ⚠ same condition
JPH2 p.Ala194Ser Uncertain significance ★★ ⚠ same condition
JPH2 p.Ala214Glu Uncertain significance ★★ ⚠ same condition
JPH2 p.Ala394Thr Uncertain significance ★★ ⚠ same condition
JPH2 p.Ala401Val Uncertain significance ★★ ⚠ same condition
JPH2 p.Ala405Thr Uncertain significance ★★ 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/jph2-p-thr287 (accessed [today's date]).

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