Is JPH3 p.Ser230= (c.690C>G) pathogenic?

JPH3 p.Ser230= (c.690C>G) is classified Likely benign in JPH3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-08). Ultra-rare (popmax 0.0207%, nfe); Associated with Inborn genetic diseases.

What condition is associated with JPH3 p.Ser230= (c.690C>G)?

JPH3 p.Ser230= (c.690C>G) is associated with Inborn genetic diseases (ClinVar).

How common is JPH3 p.Ser230= (c.690C>G) in the general population?

JPH3 p.Ser230= (c.690C>G) is ultra-rare (popmax 0.0207%, nfe) (gnomAD).

JPH3 p.Ser230=

c.690C>G · VCV4622427

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0207%, nfe)

Conditions

Inborn genetic diseases

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 1.8	GERP -0.62, phastCons 1
Overall
CADD	8.202	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0207% European (non-Finnish) · 244/1,179,812 alleles

Filtering AF 0.0185% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0177%

Overall 0.0162% 262/1,612,686 alleles · ultra-rare exomes 253/1,460,650 · genomes 9/152,036 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0207%	4,835
African / African-American	0.0107%	9,359
Remaining individualsnot grpmax-eligible	0.00961%	10,410
Finnishnot grpmax-eligible	0.00634%	15,772

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.Ser230=
Coding: c.690C>G
MANE Select: NM_020655
Type: single nucleotide variant
Location: chr16:87644565 (GRCh38)
Gene constraint: LOEUF 0.36 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 61.52
Residue 230: the 'disordered' region

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

JPH3 p.Leu266Val Uncertain significance ★★ ⚠ same condition
JPH3 p.Thr175Met Uncertain significance ★★ ⚠ same condition
JPH3 p.Gly345Ser Benign/Likely benign ★★ same condition
JPH3 p.Thr285= Likely benign ★★ same condition
JPH3 p.Ala154Thr Uncertain significance ★ ⚠ same condition
JPH3 p.Ala181Val Uncertain significance ★ ⚠ same condition
JPH3 p.Ala184Val Uncertain significance ★ ⚠ same condition
JPH3 p.Ala186Asp Conflicting classifications of pathogenicity ★ ⚠ 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-ser230 (accessed [today's date]).

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