Is CCNJL p.Val85Leu (c.253G>T) pathogenic?

CCNJL p.Val85Leu (c.253G>T) is classified Uncertain significance in CCNJL (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-22). AlphaMissense: ambiguous (0.3476); Very rare (popmax 0.000169%, nfe).

How common is CCNJL p.Val85Leu (c.253G>T) in the general population?

CCNJL p.Val85Leu (c.253G>T) is very rare (popmax 0.000169%, nfe) (gnomAD).

What do computational predictors say about CCNJL p.Val85Leu (c.253G>T)?

AlphaMissense predicts ambiguous (score 0.3476) — an in-silico prediction, not a clinical call.

CCNJL p.Val85Leu

c.253G>T · VCV4650091

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3476 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000169%, nfe)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3476	ambiguous
REVEL	0.036	moderately benign-leaning
SaProt	LLR -4.71	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.1	GERP 0.18, phastCons 0.54
Regional constraint	o/e 1.02	unconstrained · MANE · 59 kb · p 0.58 · regional, not allelic
Overall
CADD	17.53	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 0.000169% European (non-Finnish) · 2/1,179,960 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000137% 2/1,460,808 alleles · very rare

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: CCNJL
Protein: p.Val85Leu
Coding: c.253G>T
MANE Select: NM_001308173
Type: single nucleotide variant
Location: chr5:160280552 (GRCh38)
Gene constraint: LOEUF 1.263 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.40
Residue 85: the cyclin n-terminal domain

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

Similar variants

CCNJL p.Val85Met Uncertain significance ★ ⚠ same residue
CCNJL p.Ala148Thr Uncertain significance ★ ⚠ same type
CCNJL p.Ala207Ser Uncertain significance ★ ⚠ same type
CCNJL p.Ala266Thr Uncertain significance ★ ⚠ same type
CCNJL p.Ala284Val Uncertain significance ★ ⚠ same type
CCNJL p.Ala292Gly Uncertain significance ★ ⚠ same type
CCNJL p.Ala292Val Uncertain significance ★ ⚠ same type
CCNJL p.Ala356Val 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/ccnjl-p-val85leu (accessed [today's date]).

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