Is JPH2 p.Thr477= (c.1431C>T) pathogenic?

JPH2 p.Thr477= (c.1431C>T) is classified Likely benign in JPH2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-04-18). Ultra-rare (popmax 0.0239%, mid); Associated with Cardiovascular phenotype.

What condition is associated with JPH2 p.Thr477= (c.1431C>T)?

JPH2 p.Thr477= (c.1431C>T) is associated with Cardiovascular phenotype (ClinVar).

How common is JPH2 p.Thr477= (c.1431C>T) in the general population?

JPH2 p.Thr477= (c.1431C>T) is ultra-rare (popmax 0.0239%, mid) (gnomAD).

JPH2 p.Thr477=

c.1431C>T · rs1057524121 · VCV391522

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0239%, mid)

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 1.6	GERP -1.4, phastCons 1
Overall
CADD	9.938	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0239% Middle Eastern · 1/4,184 alleles

Filtering AF 0.001% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000827%

Overall 0.00142% 21/1,478,226 alleles · ultra-rare exomes 20/1,326,148 · genomes 1/152,078 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0239%	4,184
East Asian	0.00272%	36,786
European (non-Finnish)	0.0016%	62,345
South Asian	0.00132%	75,776

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.Thr477=
Coding: c.1431C>T
MANE Select: NM_020433
dbSNP: rs1057524121
Type: single nucleotide variant
Location: chr20:44116244 (GRCh38)
Gene constraint: LOEUF 1.051 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 65.09 · 2 PDB
Residue 477: the 'disordered' region; a modified residue (phosphothreonine); 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

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

Similar variants

JPH2 p.Thr477Ser Uncertain significance ★★ ⚠ same residue
JPH2 p.Thr477Asn 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-thr477 (accessed [today's date]).

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