Is JPH2 p.Pro480= (c.1440C>T) pathogenic?

JPH2 p.Pro480= (c.1440C>T) is classified Likely benign in JPH2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-09-19). Ultra-rare (popmax 0.054%, eas); Associated with hypertrophic cardiomyopathy.

What condition is associated with JPH2 p.Pro480= (c.1440C>T)?

JPH2 p.Pro480= (c.1440C>T) is associated with hypertrophic cardiomyopathy (ClinVar).

How common is JPH2 p.Pro480= (c.1440C>T) in the general population?

JPH2 p.Pro480= (c.1440C>T) is ultra-rare (popmax 0.054%, eas) (gnomAD).

JPH2 p.Pro480=

c.1440C>T · rs543997315 · VCV1772698

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.054%, eas)

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 -2.9	GERP -1.6
Overall
CADD	1.706	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.054% East Asian · 19/35,216 alleles

Filtering AF 0.0353% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0293%

Overall 0.00174% 25/1,435,980 alleles · ultra-rare exomes 22/1,283,972 · genomes 3/152,008 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.054%	1,853
South Asian	0.00145%	68,750
European (non-Finnish)	0.000452%	220,997

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.Pro480=
Coding: c.1440C>T
MANE Select: NM_020433
dbSNP: rs543997315
Type: single nucleotide variant
Location: chr20:44116235 (GRCh38)
Gene constraint: LOEUF 1.051 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 65.09 · 2 PDB
Residue 480: 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

hypertrophic cardiomyopathy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

JPH2 p.Pro480Ser 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-pro480 (accessed [today's date]).

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