Is JPH2 p.Ala260= (c.780C>T) pathogenic?

JPH2 p.Ala260= (c.780C>T) is classified Benign/Likely benign in JPH2 (ClinVar, Multiple submitters, 9 submitters; last evaluated 2025-12-14). Low-frequency (popmax 1.3%, eas); Associated with Cardiovascular phenotype.

What condition is associated with JPH2 p.Ala260= (c.780C>T)?

JPH2 p.Ala260= (c.780C>T) is associated with Cardiovascular phenotype, hypertrophic cardiomyopathy (ClinVar).

How common is JPH2 p.Ala260= (c.780C>T) in the general population?

JPH2 p.Ala260= (c.780C>T) is low-frequency (popmax 1.3%, eas) (gnomAD).

JPH2 p.Ala260=

c.780C>T · rs199840543 · VCV226677

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 9 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.3%, eas)

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -0.97	GERP -3.2
Overall
CADD	8.749	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.3% East Asian · 559/43,024 alleles

Filtering AF 1.21% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.17%

Overall 0.0382% 601/1,573,500 alleles · low-frequency exomes 530/1,421,356 · genomes 71/152,144 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	1.3%	77
South Asian	0.0288%	3,467
Remaining individualsnot grpmax-eligible	0.0228%	4,379
Middle Eastern	0.0167%	5,992
European (non-Finnish)	0.000171%	583,318

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.Ala260=
Coding: c.780C>T
MANE Select: NM_020433
dbSNP: rs199840543
Type: single nucleotide variant
Location: chr20:44160007 (GRCh38)
Gene constraint: LOEUF 1.051 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 65.09 · 2 PDB
Residue 260: 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.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
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

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-ala260 (accessed [today's date]).

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