Is JPH2 p.Pro188= (c.564C>T) pathogenic?

JPH2 p.Pro188= (c.564C>T) is classified Likely benign in JPH2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-01-07). Very rare (popmax 0.00787%, sas); Associated with Cardiovascular phenotype.

What condition is associated with JPH2 p.Pro188= (c.564C>T)?

JPH2 p.Pro188= (c.564C>T) is associated with Cardiovascular phenotype (ClinVar).

How common is JPH2 p.Pro188= (c.564C>T) in the general population?

JPH2 p.Pro188= (c.564C>T) is very rare (popmax 0.00787%, sas) (gnomAD).

JPH2 p.Pro188=

c.564C>T · rs2072600023 · VCV1748846

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00787%, sas)

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 -1	GERP -3.2
Overall
CADD	0.776	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00787% South Asian · 6/76,236 alleles

Filtering AF 0.00342% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00225%

Overall 0.000473% 7/1,480,390 alleles · very rare exomes 4/1,328,440 · genomes 3/151,950 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00787%	12,706
European (non-Finnish)	8.91e-05%	1,121,724

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.Pro188=
Coding: c.564C>T
MANE Select: NM_020433
dbSNP: rs2072600023
Type: single nucleotide variant
Location: chr20:44160223 (GRCh38)
Gene constraint: LOEUF 1.051 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 65.09 · 2 PDB
Residue 188: 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

Similar variants

JPH2 p.Pro188Ser Benign/Likely benign ★★ same residue
JPH2 p.Pro188Leu Uncertain significance ★ ⚠ same residue
JPH2 c.-4T>A Uncertain significance ★★ same condition
JPH2 p.Ala214Glu Uncertain significance ★★ ⚠ same condition
JPH2 p.Ala23Thr Uncertain significance ★★ ⚠ same condition
JPH2 p.Ala23Val Uncertain significance ★★ ⚠ same condition
JPH2 p.Ala394Thr Uncertain significance ★★ ⚠ same condition
JPH2 p.Ala401Val 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-pro188 (accessed [today's date]).

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