Is CCNG2 p.Met311Lys (c.932T>A) pathogenic?

CCNG2 p.Met311Lys (c.932T>A) is classified Uncertain significance in CCNG2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-22). AlphaMissense: ambiguous (0.3469); Ultra-rare (popmax 0.0158%, sas).

How common is CCNG2 p.Met311Lys (c.932T>A) in the general population?

CCNG2 p.Met311Lys (c.932T>A) is ultra-rare (popmax 0.0158%, sas) (gnomAD).

What do computational predictors say about CCNG2 p.Met311Lys (c.932T>A)?

AlphaMissense predicts ambiguous (score 0.3469) — an in-silico prediction, not a clinical call.

CCNG2 p.Met311Lys

c.932T>A · rs201736578 · VCV2329241

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3469 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0158%, sas)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3469	ambiguous
REVEL	0.102	moderately benign-leaning
SaProt	LLR -6.42	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 4.2	phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 7,388 bp · p 0.097 · regional, not allelic
Overall
CADD	21.6	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 0.0158% South Asian · 14/88,562 alleles

Filtering AF 0.00955% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00765%

Overall 0.00112% 18/1,601,260 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0158%	6,326
African / African-American	0.00135%	74,078
European (non-Finnish)	0.000255%	391,980

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.Met311Lys
Coding: c.932T>A
MANE Select: NM_004354
dbSNP: rs201736578
Type: single nucleotide variant
Location: chr4:77165821 (GRCh38)
Gene constraint: LOEUF 0.638 · pLI 0.57 (gnomAD)
Structure: AlphaFold pLDDT 80.23
Residue 311: the 'disordered' region

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

Similar variants

CCNG2 p.Met311Thr Uncertain significance ★ ⚠ same residue
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

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-met311lys (accessed [today's date]).

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