Is JPH2 p.Arg197Pro (c.590G>C) pathogenic?

JPH2 p.Arg197Pro (c.590G>C) is classified Uncertain significance in JPH2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-05). AlphaMissense: likely pathogenic (0.9243); No allele count reported in gnomAD v4.1 (AN 1,403,092); Associated with hypertrophic cardiomyopathy.

What condition is associated with JPH2 p.Arg197Pro (c.590G>C)?

JPH2 p.Arg197Pro (c.590G>C) is associated with hypertrophic cardiomyopathy (ClinVar).

How common is JPH2 p.Arg197Pro (c.590G>C) in the general population?

JPH2 p.Arg197Pro (c.590G>C) is no allele count reported in gnomAD v4.1 (AN 1,403,092) (gnomAD).

What do computational predictors say about JPH2 p.Arg197Pro (c.590G>C)?

AlphaMissense predicts likely pathogenic (score 0.9243) — an in-silico prediction, not a clinical call.

JPH2 p.Arg197Pro

c.590G>C · VCV3648247

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9243 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,403,092)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

hypertrophic cardiomyopathy

Computational evidence

Protein change
AlphaMissense	0.9243	likely pathogenic
REVEL	0.559	indeterminate
SaProt	LLR -6.00	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.5	GERP 1.8, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 72 kb · p 0.022 · regional, not allelic
Overall
CADD	25.6	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

No allele count reported in gnomAD v4.1 (AN 1,403,092). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: JPH2
Protein: p.Arg197Pro
Coding: c.590G>C
MANE Select: NM_020433
Type: single nucleotide variant
Location: chr20:44160197 (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.Arg197His Uncertain significance ★★ ⚠ same residue
JPH2 p.Arg197Leu Uncertain significance ★★ ⚠ same residue
JPH2 p.Arg197Cys Uncertain significance ★★ ⚠ same residue
JPH2 p.Arg197= Likely benign ★ 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

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-arg197pro (accessed [today's date]).

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