Is CCNJL p.Val191Phe (c.571G>T) pathogenic?

CCNJL p.Val191Phe (c.571G>T) is classified Uncertain significance in CCNJL (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-10). AlphaMissense: ambiguous (0.4386); Very rare (popmax 0.00334%, amr).

How common is CCNJL p.Val191Phe (c.571G>T) in the general population?

CCNJL p.Val191Phe (c.571G>T) is very rare (popmax 0.00334%, amr) (gnomAD).

What do computational predictors say about CCNJL p.Val191Phe (c.571G>T)?

AlphaMissense predicts ambiguous (score 0.4386) — an in-silico prediction, not a clinical call.

CCNJL p.Val191Phe

c.571G>T · VCV3829133

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4386 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00334%, amr)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4386	ambiguous
REVEL	0.192	benign-leaning
SaProt	LLR -7.54	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 4	GERP 2.4, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 59 kb · p 0.58 · regional, not allelic
Overall
CADD	23.2	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 V239F vs ClinVar V191F) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00334% Admixed American · 2/59,948 alleles

Filtering AF 0.00111% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0009%

Overall 0.00136% 22/1,612,378 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00334%	29,974
European (non-Finnish)	0.0017%	58,956

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.Val191Phe
Coding: c.571G>T
MANE Select: NM_001308173
Type: single nucleotide variant
Location: chr5:160259481 (GRCh38)
Gene constraint: LOEUF 1.263 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.40
Residue 191: the cyclin n-terminal domain

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-val191phe (accessed [today's date]).

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