Is CCNG2 p.Leu18Ile (c.52C>A) pathogenic?

CCNG2 p.Leu18Ile (c.52C>A) is classified Uncertain significance in CCNG2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-04-13). AlphaMissense: likely benign (0.0978); Very rare (popmax 0.00133%, afr).

How common is CCNG2 p.Leu18Ile (c.52C>A) in the general population?

CCNG2 p.Leu18Ile (c.52C>A) is very rare (popmax 0.00133%, afr) (gnomAD).

What do computational predictors say about CCNG2 p.Leu18Ile (c.52C>A)?

AlphaMissense predicts likely benign (score 0.0978) — an in-silico prediction, not a clinical call.

CCNG2 p.Leu18Ile

c.52C>A · rs761779386 · VCV2283924

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0978 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0978	likely benign
REVEL	0.019	moderately benign-leaning
SaProt	LLR -7.86	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 2.7	phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 7,388 bp · p 0.097 · regional, not allelic
Overall
CADD	19.02	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 0.00133% African / African-American · 1/74,912 alleles

Overall 0.000657% 1/152,166 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: CCNG2
Protein: p.Leu18Ile
Coding: c.52C>A
MANE Select: NM_004354
dbSNP: rs761779386
Type: single nucleotide variant
Location: chr4:77158584 (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-leu18ile (accessed [today's date]).

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