Is CCNT2 p.Leu684= (c.2052C>T) pathogenic?

CCNT2 p.Leu684= (c.2052C>T) is classified Likely benign in CCNT2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-26). Ultra-rare (popmax 0.0334%, eas).

How common is CCNT2 p.Leu684= (c.2052C>T) in the general population?

CCNT2 p.Leu684= (c.2052C>T) is ultra-rare (popmax 0.0334%, eas) (gnomAD).

CCNT2 p.Leu684=

c.2052C>T · VCV3487511

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0334%, eas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.08	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 2, phastCons 1
Overall
CADD	13.89	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0334% East Asian · 15/44,896 alleles

Filtering AF 0.0206% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0166%

Overall 0.00273% 44/1,614,000 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0334%	2,993
Remaining individualsnot grpmax-eligible	0.0032%	31,242
European (non-Finnish)	0.00229%	43,703

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: CCNT2
Protein: p.Leu684=
Coding: c.2052C>T
MANE Select: NM_058241
Type: single nucleotide variant
Location: chr2:134954507 (GRCh38)
Gene constraint: LOEUF 0.428 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 59.93 · 1 PDB

Full CCNT2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCNT2 p.Asp717Asn Uncertain significance ★★ ⚠ same type
CCNT2 p.Ala335Ser Uncertain significance ★ ⚠ same type
CCNT2 p.Ala458Thr Uncertain significance ★ ⚠ same type
CCNT2 p.Arg255Gln Uncertain significance ★ ⚠ same type
CCNT2 p.Arg255Ter Uncertain significance ★ same type
CCNT2 p.Asn208Asp Uncertain significance ★ ⚠ same type
CCNT2 p.Asn700Ser Uncertain significance ★ ⚠ same type
CCNT2 p.Asn729Ser 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/ccnt2-p-leu684 (accessed [today's date]).

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