Is JPH2 p.Ile379= (c.1137C>A) pathogenic?

JPH2 p.Ile379= (c.1137C>A) is classified Benign/Likely benign in JPH2 (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-03-01). Rare (popmax 0.475%, amr); Associated with Cardiovascular phenotype.

What condition is associated with JPH2 p.Ile379= (c.1137C>A)?

JPH2 p.Ile379= (c.1137C>A) is associated with Cardiovascular phenotype, hypertrophic cardiomyopathy (ClinVar).

How common is JPH2 p.Ile379= (c.1137C>A) in the general population?

JPH2 p.Ile379= (c.1137C>A) is rare (popmax 0.475%, amr) (gnomAD).

JPH2 p.Ile379=

c.1137C>A · rs143158930 · VCV384449

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

rare (popmax 0.475%, amr)

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -2.7	GERP -3.9
Overall
CADD	0.453	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.475% Admixed American · 285/60,004 alleles

Filtering AF 0.43% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.412%

Overall 0.0206% 331/1,607,916 alleles · rare exomes 261/1,455,558 · genomes 70/152,358 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.475%	211
Remaining individualsnot grpmax-eligible	0.0352%	2,838
African / African-American	0.0267%	3,752
Finnishnot grpmax-eligible	0.00172%	58,084
European (non-Finnish)	0.000254%	393,298

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.Ile379=
Coding: c.1137C>A
MANE Select: NM_020433
dbSNP: rs143158930
Type: single nucleotide variant
Location: chr20:44159650 (GRCh38)
Gene constraint: LOEUF 1.051 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 65.09 · 2 PDB
Residue 379: an α-helix

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

Disease context

Cardiovascular phenotype — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: hypertrophic cardiomyopathy

Similar variants

JPH2 p.Ile379Thr Uncertain significance ★ same residue
JPH2 p.Ile379Val Uncertain significance ★ ⚠ same residue
JPH2 p.Thr161Lys Pathogenic/Likely pathogenic ★★ same condition
JPH2 c.-4T>A Uncertain significance ★★ 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.Ala23Thr 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-ile379 (accessed [today's date]).

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