Is JPH2 p.Phe200Val (c.598T>G) pathogenic?

JPH2 p.Phe200Val (c.598T>G) is classified Uncertain significance in JPH2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-01). AlphaMissense: likely pathogenic (0.9972); Very rare (popmax 7.15e-05%); Associated with dilated cardiomyopathy.

What condition is associated with JPH2 p.Phe200Val (c.598T>G)?

JPH2 p.Phe200Val (c.598T>G) is associated with dilated cardiomyopathy (ClinVar).

How common is JPH2 p.Phe200Val (c.598T>G) in the general population?

JPH2 p.Phe200Val (c.598T>G) is very rare (popmax 7.15e-05%) (gnomAD).

What do computational predictors say about JPH2 p.Phe200Val (c.598T>G)?

AlphaMissense predicts likely pathogenic (score 0.9972) — an in-silico prediction, not a clinical call.

JPH2 p.Phe200Val

c.598T>G · rs2515745055 · VCV2505334

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9972 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 7.15e-05%)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

dilated cardiomyopathy

Computational evidence

Protein change
AlphaMissense	0.9972	likely pathogenic · top 8% in JPH2
REVEL	0.505	indeterminate
SaProt	LLR -4.25	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 10	GERP 1.8, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 72 kb · p 0.022 · regional, not allelic
Overall
CADD	24.1	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

Grpmax group 7.15e-05%

Overall 7.15e-05% 1/1,398,462 alleles · very rare exomes 1/1,246,802 · genomes 0/151,660 · joint denominator

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.Phe200Val
Coding: c.598T>G
MANE Select: NM_020433
dbSNP: rs2515745055
Type: single nucleotide variant
Location: chr20:44160189 (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

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

Similar variants

JPH2 p.Phe200Ser Uncertain significance ★ ⚠ same residue
JPH2 p.Arg93His Uncertain significance ★★ ⚠ same condition
JPH2 p.Arg160His Conflicting classifications of pathogenicity ★ ⚠ same condition
JPH2 p.Thr161Lys Pathogenic/Likely pathogenic ★★ same type
JPH2 c.1169+5G>A Uncertain significance ★★ same type
JPH2 c.-4T>A Uncertain significance ★★ same type
JPH2 c.*15A>T Uncertain significance ★★ same type
JPH2 p.Ala181Thr Uncertain significance ★★ ⚠ same type

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-phe200val (accessed [today's date]).

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