Is JPH3 p.Val367Ile (c.1099G>A) pathogenic?

JPH3 p.Val367Ile (c.1099G>A) is classified Likely benign in JPH3 (ClinVar, Single submitter, 1 submitter; last evaluated 2017-08-31). AlphaMissense: likely benign (0.0837); Rare (popmax 0.132%, sas).

How common is JPH3 p.Val367Ile (c.1099G>A) in the general population?

JPH3 p.Val367Ile (c.1099G>A) is rare (popmax 0.132%, sas) (gnomAD).

What do computational predictors say about JPH3 p.Val367Ile (c.1099G>A)?

AlphaMissense predicts likely benign (score 0.0837) — an in-silico prediction, not a clinical call.

JPH3 p.Val367Ile

c.1099G>A · rs147884034 · VCV718285

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0837 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.132%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0837	likely benign
REVEL	0.061	moderately benign-leaning
SaProt	LLR -6.35	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 5.8	GERP -5, phastCons 1
Regional constraint	o/e 1.16	unconstrained · MANE · 93 kb · p 6.9e-07 · regional, not allelic
Overall
CADD	20.3	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

Grpmax group 0.132% South Asian · 120/91,058 alleles

Filtering AF 0.113% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.105%

Overall 0.0213% 343/1,610,200 alleles · rare exomes 305/1,457,936 · genomes 38/152,264 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.132%	759
Middle Eastern	0.0826%	1,211
East Asian	0.058%	1,725
Remaining individualsnot grpmax-eligible	0.0192%	5,205
European (non-Finnish)	0.0142%	7,023
Admixed American	0.0133%	7,499
African / African-American	0.004%	25,012
Finnishnot grpmax-eligible	0.00165%	60,426

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.Val367Ile
Coding: c.1099G>A
MANE Select: NM_020655
dbSNP: rs147884034
Type: single nucleotide variant
Location: chr16:87644974 (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

Similar variants

JPH3 p.Arg319Trp Uncertain significance ★★ ⚠ same type
JPH3 p.Leu266Val Uncertain significance ★★ ⚠ same type
JPH3 p.Thr175Met Uncertain significance ★★ ⚠ same type
JPH3 c.2167-9C>G Benign/Likely benign ★★ same type
JPH3 p.Ala271= Benign/Likely benign ★★ same type
JPH3 p.Ala366= Likely benign ★★ same type
JPH3 p.Ala384= Likely benign ★★ same type
JPH3 p.Ala523= Benign/Likely benign ★★ 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/jph3-p-val367ile (accessed [today's date]).

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