Is CCNG2 p.Lys132Arg (c.395A>G) pathogenic?

CCNG2 p.Lys132Arg (c.395A>G) is classified Uncertain significance in CCNG2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-07). AlphaMissense: likely benign (0.0783); Ultra-rare (popmax 0.0242%, sas).

How common is CCNG2 p.Lys132Arg (c.395A>G) in the general population?

CCNG2 p.Lys132Arg (c.395A>G) is ultra-rare (popmax 0.0242%, sas) (gnomAD).

What do computational predictors say about CCNG2 p.Lys132Arg (c.395A>G)?

AlphaMissense predicts likely benign (score 0.0783) — an in-silico prediction, not a clinical call.

CCNG2 p.Lys132Arg

c.395A>G · rs748430206 · VCV2469798

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0783 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0242%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0783	likely benign
REVEL	0.107	moderately benign-leaning
SaProt	LLR -6.15	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 7.1	phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 7,388 bp · p 0.097 · regional, not allelic
Overall
CADD	19.86	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 0.0242% South Asian · 22/91,080 alleles

Filtering AF 0.0163% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0137%

Overall 0.00151% 22/1,461,782 alleles · ultra-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.Lys132Arg
Coding: c.395A>G
MANE Select: NM_004354
dbSNP: rs748430206
Type: single nucleotide variant
Location: chr4:77160839 (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-lys132arg (accessed [today's date]).

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