Is CCNG2 p.Leu252Pro (c.755T>C) pathogenic?

CCNG2 p.Leu252Pro (c.755T>C) is classified Uncertain significance in CCNG2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-01-26). AlphaMissense: likely pathogenic (0.9775); Absent from gnomAD v4.1.

How common is CCNG2 p.Leu252Pro (c.755T>C) in the general population?

CCNG2 p.Leu252Pro (c.755T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CCNG2 p.Leu252Pro (c.755T>C)?

AlphaMissense predicts likely pathogenic (score 0.9775) — an in-silico prediction, not a clinical call.

CCNG2 p.Leu252Pro

c.755T>C · rs2475815063 · VCV2467021

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9775 · 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	0.9775	likely pathogenic · top 4% in CCNG2
REVEL	0.609	indeterminate
SaProt	LLR -13.57	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 7.9	phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 7,388 bp · p 0.097 · regional, not allelic
Overall
CADD	27.0	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: CCNG2
Protein: p.Leu252Pro
Coding: c.755T>C
MANE Select: NM_004354
dbSNP: rs2475815063
Type: single nucleotide variant
Location: chr4:77164323 (GRCh38)
Gene constraint: LOEUF 0.638 · pLI 0.57 (gnomAD)
Structure: AlphaFold pLDDT 80.23

Full CCNG2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCNG2 p.Leu17= Benign ★★ same type
CCNG2 p.Leu280= Benign ★★ same type
CCNG2 p.Ser136= Benign ★★ same type
CCNG2 p.Ala207Ser Uncertain significance ★ ⚠ same type
CCNG2 p.Arg111Gly Uncertain significance ★ ⚠ same type
CCNG2 p.Arg111Ile Uncertain significance ★ ⚠ same type
CCNG2 p.Arg127Gln Uncertain significance ★ ⚠ same type
CCNG2 p.Arg275His 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/ccng2-p-leu252pro (accessed [today's date]).

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