Is JPH2 p.Lys229= (c.687G>A) pathogenic?

JPH2 p.Lys229= (c.687G>A) is classified Likely benign in JPH2 (ClinVar, Single submitter, 1 submitter; last evaluated 2017-12-12). Very rare (popmax 0.00198%, amr); Associated with Cardiovascular phenotype.

What condition is associated with JPH2 p.Lys229= (c.687G>A)?

JPH2 p.Lys229= (c.687G>A) is associated with Cardiovascular phenotype (ClinVar).

How common is JPH2 p.Lys229= (c.687G>A) in the general population?

JPH2 p.Lys229= (c.687G>A) is very rare (popmax 0.00198%, amr) (gnomAD).

JPH2 p.Lys229=

c.687G>A · rs1372719506 · VCV518763

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00198%, amr)

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 -0.095	GERP -3.1
Overall
CADD	6.195	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00198% Admixed American · 1/50,586 alleles

Overall 6.54e-05% 1/1,529,000 alleles · very rare exomes 1/1,377,020 · genomes 0/151,980 · 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.Lys229=
Coding: c.687G>A
MANE Select: NM_020433
dbSNP: rs1372719506
Type: single nucleotide variant
Location: chr20:44160100 (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

Cardiovascular phenotype — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

JPH2 p.Lys229Glu Uncertain significance ★ ⚠ same residue
JPH2 p.Lys229Arg 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-lys229 (accessed [today's date]).

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