Is CCNI2 p.Glu209Asp (c.627A>T) pathogenic?

CCNI2 p.Glu209Asp (c.627A>T) is classified Uncertain significance in CCNI2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-01). AlphaMissense: ambiguous (0.3863); Very rare (popmax 8.48e-05%, nfe).

How common is CCNI2 p.Glu209Asp (c.627A>T) in the general population?

CCNI2 p.Glu209Asp (c.627A>T) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

What do computational predictors say about CCNI2 p.Glu209Asp (c.627A>T)?

AlphaMissense predicts ambiguous (score 0.3863) — an in-silico prediction, not a clinical call.

CCNI2 p.Glu209Asp

c.627A>T · VCV3829127

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3863 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3863	ambiguous
REVEL	0.146	moderately benign-leaning
SaProt	LLR -7.33	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 0.065	GERP -2.8, phastCons 0.56
Regional constraint	o/e 0.93	unconstrained · MANE · 5,471 bp · p 0.12 · regional, not allelic
Overall
CADD	16.69	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,854 alleles

Overall 6.84e-05% 1/1,461,670 alleles · very 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: CCNI2
Protein: p.Glu209Asp
Coding: c.627A>T
MANE Select: NM_001039780
Type: single nucleotide variant
Location: chr5:132749416 (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-glu209asp (accessed [today's date]).

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