Is CCNG2 p.Leu227Val (c.679C>G) pathogenic?

CCNG2 p.Leu227Val (c.679C>G) is classified Uncertain significance in CCNG2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-19). AlphaMissense: likely benign (0.1014); Ultra-rare (popmax 0.0608%, sas).

How common is CCNG2 p.Leu227Val (c.679C>G) in the general population?

CCNG2 p.Leu227Val (c.679C>G) is ultra-rare (popmax 0.0608%, sas) (gnomAD).

What do computational predictors say about CCNG2 p.Leu227Val (c.679C>G)?

AlphaMissense predicts likely benign (score 0.1014) — an in-silico prediction, not a clinical call.

CCNG2 p.Leu227Val

c.679C>G · rs775445447 · VCV2462829

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1014 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0608%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1014	likely benign
REVEL	0.08	moderately benign-leaning
SaProt	LLR -7.23	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 1.5	phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 7,388 bp · p 0.097 · regional, not allelic
Overall
CADD	13.65	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 0.0608% South Asian · 54/88,882 alleles

Filtering AF 0.0478% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0431%

Overall 0.00361% 58/1,605,380 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0608%	1,646
Remaining individualsnot grpmax-eligible	0.00322%	31,085
European (non-Finnish)	0.00017%	588,343

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.Leu227Val
Coding: c.679C>G
MANE Select: NM_004354
dbSNP: rs775445447
Type: single nucleotide variant
Location: chr4:77161721 (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-leu227val (accessed [today's date]).

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