Is JPH1 p.Pro103= (c.309C>T) pathogenic?

JPH1 p.Pro103= (c.309C>T) is classified Benign in JPH1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2019-12-31). Common (popmax 8%, afr) — too common for a highly-penetrant pathogenic allele.

JPH1 p.Pro103=

Q: How common is JPH1 p.Pro103= (c.309C>T) in the general population?

JPH1 p.Pro103= (c.309C>T) is common (popmax 8%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.309C>T · rs79761162 · VCV770573

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 8%, afr) — too common for a highly-penetrant pathogenic allele

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 0.049	GERP -3.9, phastCons 0.62
Overall
CADD	11.82	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8% African / African-American · 5,977/74,756 alleles

Filtering AF 7.83% ClinGen BA1/BS1 input FAF95, joint · FAF99 7.76%

Overall 0.417% 6,721/1,610,916 alleles · common exomes 3,339/1,458,728 · genomes 3,382/152,188 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	8%	13
Remaining individualsnot grpmax-eligible	0.545%	183
Admixed American	0.489%	204
Middle Eastern	0.298%	336
South Asian	0.0221%	4,532
European (non-Finnish)	0.00628%	15,928

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: JPH1
Protein: p.Pro103=
Coding: c.309C>T
MANE Select: NM_020647
dbSNP: rs79761162
Type: single nucleotide variant
Location: chr8:74320979 (GRCh38)
Gene constraint: LOEUF 0.365 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 66.06 · 1 PDB
Residue 103: a β-strand

Full JPH1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

JPH1 p.Arg399His Uncertain significance ★★ ⚠ same type
JPH1 p.Ile404Met Uncertain significance ★★ ⚠ same type
JPH1 p.Ala525= Benign ★★ same type
JPH1 p.Lys441Arg Benign ★★ same type
JPH1 p.Lys610= Benign ★★ same type
JPH1 p.Val526Ile Benign ★★ same type
JPH1 p.Tyr118Ter Likely pathogenic ★ same type
JPH1 p.Ala183Thr 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/jph1-p-pro103 (accessed [today's date]).

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