Is CCNJ p.Thr231Ser (c.691A>T) pathogenic?

CCNJ p.Thr231Ser (c.691A>T) is classified Uncertain significance in CCNJ (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-22). AlphaMissense: ambiguous (0.4226); Absent from gnomAD v4.1.

How common is CCNJ p.Thr231Ser (c.691A>T) in the general population?

CCNJ p.Thr231Ser (c.691A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CCNJ p.Thr231Ser (c.691A>T)?

AlphaMissense predicts ambiguous (score 0.4226) — an in-silico prediction, not a clinical call.

CCNJ p.Thr231Ser

c.691A>T · VCV3487458

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4226 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4226	ambiguous
REVEL	0.05	moderately benign-leaning
SaProt	LLR -3.73	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 11	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	21.1	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 T220S vs ClinVar T231S) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CCNJ
Protein: p.Thr231Ser
Coding: c.691A>T
MANE Select: NM_001134375
Type: single nucleotide variant
Location: chr10:96057198 (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-thr231ser (accessed [today's date]).

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