Is CCNE2 p.Lys232Thr (c.695A>C) pathogenic?

CCNE2 p.Lys232Thr (c.695A>C) is classified Uncertain significance in CCNE2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-06). AlphaMissense: likely pathogenic (0.5808); Very rare (popmax 8.85e-05%, nfe).

How common is CCNE2 p.Lys232Thr (c.695A>C) in the general population?

CCNE2 p.Lys232Thr (c.695A>C) is very rare (popmax 8.85e-05%, nfe) (gnomAD).

What do computational predictors say about CCNE2 p.Lys232Thr (c.695A>C)?

AlphaMissense predicts likely pathogenic (score 0.5808) — an in-silico prediction, not a clinical call.

CCNE2 p.Lys232Thr

c.695A>C · rs753829268 · VCV2557821

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5808 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.85e-05%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.5808	likely pathogenic
REVEL	0.282	benign-leaning
SaProt	LLR -9.36	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	Δ0.27	donor loss, 1 bp away · masked 0 · deltas
Pangolin	Δ0.26	loss · gain 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 7.8	GERP 1.9, phastCons 1
Regional constraint	o/e 0.79	unconstrained · MANE · 13 kb · p 8.7e-06 · regional, not allelic
Overall
CADD	30.0	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 8.85e-05% European (non-Finnish) · 1/1,130,118 alleles

Overall 0.000573% 8/1,394,954 alleles · very rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.0245%	4,078
European (non-Finnish)grpmax	8.85e-05%	1,130,118

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: CCNE2
Protein: p.Lys232Thr
Coding: c.695A>C
MANE Select: NM_057749
dbSNP: rs753829268
Type: single nucleotide variant
Location: chr8:94885464 (GRCh38)
Gene constraint: LOEUF 0.537 · pLI 0.95 (gnomAD)
Structure: AlphaFold pLDDT 77.80 · 1 PDB

Full CCNE2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCNE2 p.Ala204Gly Uncertain significance ★ ⚠ same type
CCNE2 p.Asp222Gly Uncertain significance ★ ⚠ same type
CCNE2 p.Asp258Gly Uncertain significance ★ ⚠ same type
CCNE2 p.Glu221Lys Uncertain significance ★ ⚠ same type
CCNE2 p.Glu323Gln Uncertain significance ★ ⚠ same type
CCNE2 p.Glu323Val Uncertain significance ★ ⚠ same type
CCNE2 p.Gly402Arg Uncertain significance ★ ⚠ same type
CCNE2 p.His159Tyr 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/ccne2-p-lys232thr (accessed [today's date]).

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