Is CCNJL p.Pro286Gln (c.857C>A) pathogenic?

CCNJL p.Pro286Gln (c.857C>A) is classified Uncertain significance in CCNJL (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-21). AlphaMissense: likely benign (0.1006); Very rare (popmax 0.00017%, nfe).

How common is CCNJL p.Pro286Gln (c.857C>A) in the general population?

CCNJL p.Pro286Gln (c.857C>A) is very rare (popmax 0.00017%, nfe) (gnomAD).

What do computational predictors say about CCNJL p.Pro286Gln (c.857C>A)?

AlphaMissense predicts likely benign (score 0.1006) — an in-silico prediction, not a clinical call.

CCNJL p.Pro286Gln

c.857C>A · rs780867242 · VCV2620039

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1006 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00017%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1006	likely benign
REVEL	0.085	moderately benign-leaning
SaProt	LLR -6.83	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 4.9	GERP 0.9, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 59 kb · p 0.58 · regional, not allelic
Overall
CADD	16.34	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 P334Q vs ClinVar P286Q) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00017% European (non-Finnish) · 2/1,176,240 alleles

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

Overall 0.000933% 15/1,607,476 alleles · very rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.0376%	2,662
Remaining individualsnot grpmax-eligible	0.00322%	31,095
European (non-Finnish)grpmax	0.00017%	588,121

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Pro286Gln
Coding: c.857C>A
MANE Select: NM_001308173
dbSNP: rs780867242
Type: single nucleotide variant
Location: chr5:160253685 (GRCh38)
Gene constraint: LOEUF 1.263 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.40

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

Similar variants

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
CCNJL p.Ala366Thr 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-pro286gln (accessed [today's date]).

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