Is CCNI2 p.Val74Phe (c.220G>T) pathogenic?

CCNI2 p.Val74Phe (c.220G>T) is classified Uncertain significance in CCNI2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-12). AlphaMissense: likely benign (0.1117); Ultra-rare (popmax 0.0197%, nfe).

How common is CCNI2 p.Val74Phe (c.220G>T) in the general population?

CCNI2 p.Val74Phe (c.220G>T) is ultra-rare (popmax 0.0197%, nfe) (gnomAD).

What do computational predictors say about CCNI2 p.Val74Phe (c.220G>T)?

AlphaMissense predicts likely benign (score 0.1117) — an in-silico prediction, not a clinical call.

CCNI2 p.Val74Phe

c.220G>T · rs560447120 · VCV3139940

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1117 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0197%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1117	likely benign
REVEL	0.057	moderately benign-leaning
SaProt	LLR -8.51	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 -2	GERP 1.4
Regional constraint	o/e 0.93	unconstrained · MANE · 5,471 bp · p 0.12 · regional, not allelic
Overall
CADD	1.153	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.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0197% European (non-Finnish) · 222/1,126,646 alleles

Filtering AF 0.0175% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0167%

Overall 0.0153% 228/1,487,990 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0197%	5,075
Remaining individualsnot grpmax-eligible	0.00866%	11,553
African / African-American	0.00146%	68,706

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: CCNI2
Protein: p.Val74Phe
Coding: c.220G>T
MANE Select: NM_001039780
dbSNP: rs560447120
Type: single nucleotide variant
Location: chr5:132747715 (GRCh38)
Gene constraint: LOEUF 1.451 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.87
Residue 74: the 'disordered' region

Full CCNI2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCNI2 p.Ala2Val Uncertain significance ★ ⚠ same type
CCNI2 p.Arg108Cys Uncertain significance ★ ⚠ same type
CCNI2 p.Arg159Trp Uncertain significance ★ ⚠ same type
CCNI2 p.Arg55Ser Uncertain significance ★ ⚠ same type
CCNI2 p.Arg77Gly Uncertain significance ★ ⚠ same type
CCNI2 p.Arg79Gly Uncertain significance ★ ⚠ same type
CCNI2 p.Asp116Asn Uncertain significance ★ ⚠ same type
CCNI2 p.Asp118Glu 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/ccni2-p-val74phe (accessed [today's date]).

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