Is JPH2 p.Ser592= (c.1776C>T) pathogenic?

JPH2 p.Ser592= (c.1776C>T) is classified Likely benign in JPH2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-22). Very rare (popmax 0.000428%, nfe); Associated with Cardiovascular phenotype.

What condition is associated with JPH2 p.Ser592= (c.1776C>T)?

JPH2 p.Ser592= (c.1776C>T) is associated with Cardiovascular phenotype (ClinVar).

How common is JPH2 p.Ser592= (c.1776C>T) in the general population?

JPH2 p.Ser592= (c.1776C>T) is very rare (popmax 0.000428%, nfe) (gnomAD).

JPH2 p.Ser592=

c.1776C>T · rs763485402 · VCV1779879

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000428%, nfe)

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 0.64	GERP 1.5, phastCons 0.96
Overall
CADD	10.74	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000428% European (non-Finnish) · 5/1,167,336 alleles

Filtering AF 0.000126% ClinGen BA1/BS1 input FAF95, joint · FAF99 9.1e-05%

Overall 0.000317% 5/1,576,154 alleles · very rare exomes 5/1,423,972 · genomes 0/152,182 · 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.Ser592=
Coding: c.1776C>T
MANE Select: NM_020433
dbSNP: rs763485402
Type: single nucleotide variant
Location: chr20:44115899 (GRCh38)
Gene constraint: LOEUF 1.051 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 65.09 · 2 PDB
Residue 592: the 'disordered' region; a UniProt-annotated variant site (in cmd2e; uncertain significance)

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 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
JPH2 p.Ala419Ser Uncertain significance ★★ ⚠ same condition
JPH2 p.Ala460Val 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-ser592 (accessed [today's date]).

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