Is JPH2 p.Ser102Arg (c.306C>A) pathogenic?

JPH2 p.Ser102Arg (c.306C>A) is classified Uncertain significance in JPH2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-02). AlphaMissense: likely pathogenic (0.9932); No allele count reported in gnomAD v4.1 (AN 1,613,636); Associated with hypertrophic cardiomyopathy.

What condition is associated with JPH2 p.Ser102Arg (c.306C>A)?

JPH2 p.Ser102Arg (c.306C>A) is associated with hypertrophic cardiomyopathy (ClinVar).

How common is JPH2 p.Ser102Arg (c.306C>A) in the general population?

JPH2 p.Ser102Arg (c.306C>A) is no allele count reported in gnomAD v4.1 (AN 1,613,636) (gnomAD).

What do computational predictors say about JPH2 p.Ser102Arg (c.306C>A)?

AlphaMissense predicts likely pathogenic (score 0.9932) — an in-silico prediction, not a clinical call.

JPH2 p.Ser102Arg

c.306C>A · rs779455211 · VCV2756684

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9932 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,613,636)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hypertrophic cardiomyopathy

Computational evidence

Protein change
AlphaMissense	0.9932	likely pathogenic
REVEL	0.288	benign-leaning
SaProt	LLR -16.00	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2.4	GERP 0.83
Regional constraint	o/e 0.93	unconstrained · MANE · 72 kb · p 0.022 · regional, not allelic
Overall
CADD	22.7	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,613,636). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: JPH2
Protein: p.Ser102Arg
Coding: c.306C>A
MANE Select: NM_020433
dbSNP: rs779455211
Type: single nucleotide variant
Location: chr20:44186400 (GRCh38)
Gene constraint: LOEUF 1.051 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 65.09 · 2 PDB
Residue 102: a β-strand

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.Ser102= Likely benign ★★ same residue
JPH2 p.Ser102Cys 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

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-ser102arg (accessed [today's date]).

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