Is CCNI2 p.Thr306Pro (c.916A>C) pathogenic?

CCNI2 p.Thr306Pro (c.916A>C) is classified Uncertain significance in CCNI2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-15). AlphaMissense: likely pathogenic (0.6836); Absent from gnomAD v4.1.

How common is CCNI2 p.Thr306Pro (c.916A>C) in the general population?

CCNI2 p.Thr306Pro (c.916A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CCNI2 p.Thr306Pro (c.916A>C)?

AlphaMissense predicts likely pathogenic (score 0.6836) — an in-silico prediction, not a clinical call.

CCNI2 p.Thr306Pro

c.916A>C · rs2532012897 · VCV2484732

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6836 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.6836	likely pathogenic
REVEL	0.426	indeterminate
SaProt	LLR -13.75	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 6.6, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 5,471 bp · p 0.12 · regional, not allelic
Overall
CADD	27.9	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

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: CCNI2
Protein: p.Thr306Pro
Coding: c.916A>C
MANE Select: NM_001039780
dbSNP: rs2532012897
Type: single nucleotide variant
Location: chr5:132752107 (GRCh38)
Gene constraint: LOEUF 1.451 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.87

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-thr306pro (accessed [today's date]).

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