Is JPH2 p.Ser192= (c.576G>A) pathogenic?

JPH2 p.Ser192= (c.576G>A) is classified Likely benign in JPH2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-08-28). Ultra-rare (popmax 0.0151%, afr); Associated with Cardiovascular phenotype.

What condition is associated with JPH2 p.Ser192= (c.576G>A)?

JPH2 p.Ser192= (c.576G>A) is associated with Cardiovascular phenotype, hypertrophic cardiomyopathy (ClinVar).

How common is JPH2 p.Ser192= (c.576G>A) in the general population?

JPH2 p.Ser192= (c.576G>A) is ultra-rare (popmax 0.0151%, afr) (gnomAD).

JPH2 p.Ser192=

c.576G>A · rs1397018944 · VCV507895

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0151%, afr)

Conditions

Cardiovascular phenotype

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 0.078	GERP -0.13, phastCons 0.59
Overall
CADD	10.8	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0151% African / African-American · 10/66,336 alleles

Filtering AF 0.0081% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00613%

Overall 0.00105% 15/1,423,378 alleles · ultra-rare exomes 9/1,271,608 · genomes 6/151,770 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0151%	6,634
Remaining individualsnot grpmax-eligible	0.00549%	18,212
South Asian	0.00296%	33,769

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.Ser192=
Coding: c.576G>A
MANE Select: NM_020433
dbSNP: rs1397018944
Type: single nucleotide variant
Location: chr20:44160211 (GRCh38)
Gene constraint: LOEUF 1.051 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 65.09 · 2 PDB
Residue 192: the 'disordered' region

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.Ser192Leu Uncertain significance ★★ ⚠ same residue
JPH2 p.Ser192Ala Uncertain significance ★ ⚠ same residue
JPH2 p.Ser192Trp Uncertain significance ★ ⚠ same residue
JPH2 p.Ser192Ter Likely pathogenic ★ 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

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-ser192 (accessed [today's date]).

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