Is CCNJ p.His284Asp (c.850C>G) pathogenic?

CCNJ p.His284Asp (c.850C>G) is classified Uncertain significance in CCNJ (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-13). AlphaMissense: likely benign (0.1296); Ultra-rare (popmax 0.0133%, amr).

How common is CCNJ p.His284Asp (c.850C>G) in the general population?

CCNJ p.His284Asp (c.850C>G) is ultra-rare (popmax 0.0133%, amr) (gnomAD).

What do computational predictors say about CCNJ p.His284Asp (c.850C>G)?

AlphaMissense predicts likely benign (score 0.1296) — an in-silico prediction, not a clinical call.

CCNJ p.His284Asp

c.850C>G · VCV3487451

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1296 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0133%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1296	likely benign
REVEL	0.132	moderately benign-leaning
SaProt	LLR -7.70	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 7.7	GERP 1.9, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 991 bp · p 0.48 · regional, not allelic
Overall
CADD	20.7	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 H273D vs ClinVar H284D) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0133% Admixed American · 8/60,032 alleles

Filtering AF 0.00661% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00482%

Overall 0.000547% 8/1,461,888 alleles · ultra-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: CCNJ
Protein: p.His284Asp
Coding: c.850C>G
MANE Select: NM_001134375
Type: single nucleotide variant
Location: chr10:96057939 (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-his284asp (accessed [today's date]).

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