Is CCNJ p.Arg218Pro (c.653G>C) pathogenic?

CCNJ p.Arg218Pro (c.653G>C) is classified Uncertain significance in CCNJ (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-28). AlphaMissense: likely pathogenic (0.9854); Very rare (popmax 0.00267%, afr).

How common is CCNJ p.Arg218Pro (c.653G>C) in the general population?

CCNJ p.Arg218Pro (c.653G>C) is very rare (popmax 0.00267%, afr) (gnomAD).

What do computational predictors say about CCNJ p.Arg218Pro (c.653G>C)?

AlphaMissense predicts likely pathogenic (score 0.9854) — an in-silico prediction, not a clinical call.

CCNJ p.Arg218Pro

c.653G>C · VCV3997664

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9854 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9854	likely pathogenic
REVEL	0.225	benign-leaning
SaProt	LLR -10.81	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.8	GERP 1.8, phastCons 1
Regional constraint	o/e 0.54	unconstrained · MANE · 6,946 bp · p 3.2e-13 · regional, not allelic
Overall
CADD	29.2	PHRED · no single calibrated threshold — expert panels disagree

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM R207P vs ClinVar R218P) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00267% African / African-American · 2/74,888 alleles

Filtering AF 0.000443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.000186% 3/1,613,780 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00267%	37,444
Finnishnot grpmax-eligible	0.00156%	64,002

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.Arg218Pro
Coding: c.653G>C
MANE Select: NM_001134375
Type: single nucleotide variant
Location: chr10:96057160 (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.Arg218His Uncertain significance ★ ⚠ same residue
CCNJ p.Ala158Gly Uncertain significance ★ ⚠ same type
CCNJ p.Ala232Val Uncertain significance ★ ⚠ same type
CCNJ p.Ala60Thr 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
CCNJ p.Arg53His 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-arg218pro (accessed [today's date]).

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