Is JPH2 p.Ala270= (c.810C>A) pathogenic?

JPH2 p.Ala270= (c.810C>A) is classified Likely benign in JPH2 (ClinVar, Multiple submitters, 7 submitters; last evaluated 2024-03-21). Very rare (popmax 0.00264%, nfe); Associated with Cardiovascular phenotype.

What condition is associated with JPH2 p.Ala270= (c.810C>A)?

JPH2 p.Ala270= (c.810C>A) is associated with Cardiovascular phenotype, hypertrophic cardiomyopathy, hypertrophic cardiomyopathy 17 (ClinVar).

How common is JPH2 p.Ala270= (c.810C>A) in the general population?

JPH2 p.Ala270= (c.810C>A) is very rare (popmax 0.00264%, nfe) (gnomAD).

JPH2 p.Ala270=

c.810C>A · rs779680763 · VCV518319

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00264%, 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 -0.2	GERP -0.62, phastCons 0.068
Overall
CADD	6.612	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00264% European (non-Finnish) · 31/1,173,468 alleles

Filtering AF 0.00189% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00165%

Overall 0.00195% 31/1,591,706 alleles · very rare exomes 29/1,439,750 · genomes 2/151,956 · 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.Ala270=
Coding: c.810C>A
MANE Select: NM_020433
dbSNP: rs779680763
Type: single nucleotide variant
Location: chr20:44159977 (GRCh38)
Gene constraint: LOEUF 1.051 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 65.09 · 2 PDB
Residue 270: 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 hypertrophic cardiomyopathy 17

Similar variants

JPH2 p.Thr161Lys Pathogenic/Likely pathogenic ★★ same condition
JPH2 c.-4T>A Uncertain significance ★★ same condition
JPH2 c.*15A>T 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

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-ala270 (accessed [today's date]).

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