Is CCNJ p.Val336Ile (c.1006G>A) pathogenic?

CCNJ p.Val336Ile (c.1006G>A) is classified Uncertain significance in CCNJ (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-18). AlphaMissense: likely benign (0.0655); Rare (popmax 0.105%, amr).

How common is CCNJ p.Val336Ile (c.1006G>A) in the general population?

CCNJ p.Val336Ile (c.1006G>A) is rare (popmax 0.105%, amr) (gnomAD).

What do computational predictors say about CCNJ p.Val336Ile (c.1006G>A)?

AlphaMissense predicts likely benign (score 0.0655) — an in-silico prediction, not a clinical call.

CCNJ p.Val336Ile

c.1006G>A · VCV3487450

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0655 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.105%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0655	likely benign
REVEL	0.027	moderately benign-leaning
SaProt	LLR -7.24	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 9.9	GERP 1.9, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 991 bp · p 0.48 · regional, not allelic
Overall
CADD	21.0	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.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM V325I vs ClinVar V336I) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.105% Admixed American · 63/60,006 alleles

Filtering AF 0.0841% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0766%

Overall 0.00409% 66/1,614,042 alleles · rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.105%	952
Remaining individualsnot grpmax-eligible	0.0048%	20,828

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: CCNJ
Protein: p.Val336Ile
Coding: c.1006G>A
MANE Select: NM_001134375
Type: single nucleotide variant
Location: chr10:96058095 (GRCh38)
Gene constraint: LOEUF 0.497 · pLI 0.98 (gnomAD)
Structure: AlphaFold pLDDT 73.34

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

Similar variants

CCNJ p.Ala158Gly Uncertain significance ★ ⚠ same type
CCNJ p.Ala232Val Uncertain significance ★ ⚠ same type
CCNJ p.Ala60Thr Uncertain significance ★ ⚠ same type
CCNJ p.Arg218His Uncertain significance ★ ⚠ same type
CCNJ p.Arg218Pro Uncertain significance ★ ⚠ same type
CCNJ p.Arg229Cys Uncertain significance ★ ⚠ same type
CCNJ p.Arg281Gln Uncertain significance ★ ⚠ same type
CCNJ p.Arg281Trp 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/ccnj-p-val336ile (accessed [today's date]).

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