Is JPH2 p.Val246= (c.738C>G) pathogenic?

JPH2 p.Val246= (c.738C>G) is classified Likely benign in JPH2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-21). Very rare (popmax 0.000347%, nfe); Associated with hypertrophic cardiomyopathy.

What condition is associated with JPH2 p.Val246= (c.738C>G)?

JPH2 p.Val246= (c.738C>G) is associated with hypertrophic cardiomyopathy (ClinVar).

How common is JPH2 p.Val246= (c.738C>G) in the general population?

JPH2 p.Val246= (c.738C>G) is very rare (popmax 0.000347%, nfe) (gnomAD).

JPH2 p.Val246=

c.738C>G · rs2515744791 · VCV2985956

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000347%, nfe)

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	GERP -3.5, phastCons 1
Overall
CADD	8.778	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000347% European (non-Finnish) · 4/1,154,140 alleles

Filtering AF 8.1e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.5e-05%

Overall 0.000258% 4/1,549,682 alleles · very rare exomes 4/1,397,492 · genomes 0/152,190 · 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.Val246=
Coding: c.738C>G
MANE Select: NM_020433
dbSNP: rs2515744791
Type: single nucleotide variant
Location: chr20:44160049 (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.Val246Ile 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-val246 (accessed [today's date]).

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