Is JPH2 p.Arg313His (c.938G>A) pathogenic?

JPH2 p.Arg313His (c.938G>A) is classified Uncertain significance in JPH2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-11). AlphaMissense: likely benign (0.1113); Absent from gnomAD v4.1.

How common is JPH2 p.Arg313His (c.938G>A) in the general population?

JPH2 p.Arg313His (c.938G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about JPH2 p.Arg313His (c.938G>A)?

AlphaMissense predicts likely benign (score 0.1113) — an in-silico prediction, not a clinical call.

JPH2 p.Arg313His

c.938G>A · VCV3903169

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1113 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1113	likely benign
REVEL	0.132	moderately benign-leaning
SaProt	LLR -12.95	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 4.6	GERP -3.9, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 72 kb · p 0.022 · regional, not allelic
Overall
CADD	27.9	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: JPH2
Protein: p.Arg313His
Coding: c.938G>A
MANE Select: NM_020433
Type: single nucleotide variant
Location: chr20:44159849 (GRCh38)
Gene constraint: LOEUF 1.051 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 65.09 · 2 PDB
Residue 313: a β-strand

Full JPH2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

JPH2 p.Arg313Cys Uncertain significance ★ ⚠ same residue
JPH2 p.Arg313= Likely benign ★ same residue
JPH2 p.Thr161Lys Pathogenic/Likely pathogenic ★★ same type
JPH2 c.1169+5G>A Uncertain significance ★★ same type
JPH2 c.-4T>A Uncertain significance ★★ same type
JPH2 c.*15A>T Uncertain significance ★★ same type
JPH2 p.Ala181Thr Uncertain significance ★★ ⚠ same type
JPH2 p.Ala194Ser Uncertain significance ★★ ⚠ same type

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-arg313his (accessed [today's date]).

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