Is JPH3 p.Pro472Ser (c.1414C>T) pathogenic?

JPH3 p.Pro472Ser (c.1414C>T) is classified Uncertain significance in JPH3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-14). AlphaMissense: likely benign (0.3068); Very rare (popmax 0.0084%, nfe); Associated with Inborn genetic diseases.

What condition is associated with JPH3 p.Pro472Ser (c.1414C>T)?

JPH3 p.Pro472Ser (c.1414C>T) is associated with Inborn genetic diseases (ClinVar).

How common is JPH3 p.Pro472Ser (c.1414C>T) in the general population?

JPH3 p.Pro472Ser (c.1414C>T) is very rare (popmax 0.0084%, nfe) (gnomAD).

What do computational predictors say about JPH3 p.Pro472Ser (c.1414C>T)?

AlphaMissense predicts likely benign (score 0.3068) — an in-silico prediction, not a clinical call.

JPH3 p.Pro472Ser

c.1414C>T · rs17853660 · VCV3112476

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3068 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0084%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3068	likely benign
REVEL	0.262	benign-leaning
SaProt	LLR -7.27	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.7	GERP 1.2, phastCons 1
Regional constraint	o/e 1.16	unconstrained · MANE · 93 kb · p 6.9e-07 · regional, not allelic
Overall
CADD	26.3	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0084% European (non-Finnish) · 99/1,178,644 alleles

Filtering AF 0.00703% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00652%

Overall 0.00634% 102/1,609,946 alleles · very rare exomes 99/1,457,764 · genomes 3/152,182 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0084%	11,905
Remaining individualsnot grpmax-eligible	0.00482%	20,763

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.Pro472Ser
Coding: c.1414C>T
MANE Select: NM_020655
dbSNP: rs17853660
Type: single nucleotide variant
Location: chr16:87689774 (GRCh38)
Gene constraint: LOEUF 0.36 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 61.52
Residue 472: the 'disordered' region; a UniProt-annotated variant site (in)

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-pro472ser (accessed [today's date]).

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