Is JPH3 p.Arg320= (c.960C>T) pathogenic?

JPH3 p.Arg320= (c.960C>T) is classified Benign in JPH3 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-10-21). Common (popmax 18.4%, mid) — too common for a highly-penetrant pathogenic allele; Associated with JPH3-related disorder.

What condition is associated with JPH3 p.Arg320= (c.960C>T)?

JPH3 p.Arg320= (c.960C>T) is associated with JPH3-related disorder (ClinVar).

JPH3 p.Arg320=

Q: How common is JPH3 p.Arg320= (c.960C>T) in the general population?

JPH3 p.Arg320= (c.960C>T) is common (popmax 18.4%, mid) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.960C>T · rs8051448 · VCV3057021

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Common

common (popmax 18.4%, mid) — too common for a highly-penetrant pathogenic allele

Conditions

JPH3-related disorder

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 0.23	GERP -5.8, phastCons 0.98
Overall
CADD	6.303	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 18.4% Middle Eastern · 1,117/6,062 alleles

Filtering AF 18% ClinGen BA1/BS1 input FAF95, joint · FAF99 17.9%

Overall 13.5% 217,221/1,613,292 alleles · common exomes 197,625/1,461,244 · genomes 19,596/152,048 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	18.4%	5
South Asian	18.2%	5
African / African-American	14.7%	7
European (non-Finnish)	14%	7
Remaining individualsnot grpmax-eligible	13.4%	7
Ashkenazi Jewishnot grpmax-eligible	13.3%	8
Finnishnot grpmax-eligible	9.03%	11
Admixed American	7.76%	13
Amishnot grpmax-eligible	6.48%	15
East Asian	1.21%	82

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: JPH3
Protein: p.Arg320=
Coding: c.960C>T
MANE Select: NM_020655
dbSNP: rs8051448
Type: single nucleotide variant
Location: chr16:87644835 (GRCh38)
Gene constraint: LOEUF 0.36 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 61.52

Full JPH3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

JPH3-related disorder

Similar variants

JPH3 p.Arg320His Uncertain significance ★ ⚠ same residue
JPH3 c.382+635C>T Likely benign same condition
JPH3 p.Ala154Pro Likely benign same condition
JPH3 p.Ala190= Likely benign same condition
JPH3 p.Asn103= Likely benign same condition
JPH3 p.Asp641Tyr Likely benign same condition
JPH3 p.Ile280= Likely benign same condition
JPH3 p.Leu177= Likely benign 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/jph3-p-arg320 (accessed [today's date]).

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