Is CCNT2 p.Arg255Ter (c.763C>T) pathogenic?

CCNT2 p.Arg255Ter (c.763C>T) is classified Uncertain significance in CCNT2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-06-17). Absent from gnomAD v4.1.

How common is CCNT2 p.Arg255Ter (c.763C>T) in the general population?

CCNT2 p.Arg255Ter (c.763C>T) is absent from gnomAD v4.1 (gnomAD).

CCNT2 p.Arg255Ter

c.763C>T · VCV4956766

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function in a LoF-intolerant gene
NMD	escapes	premature termination codon within the last 50 nt of the penultimate exon (8 of 9, 11 nt from its 3' end) — the truncated protein is likely expressed. PVS1 input, not an applied code
REVEL	0.134	moderately benign-leaning
Splicing
SpliceAI	Δ0.21	donor loss · deltas
Pangolin	Δ0.31	loss · gain 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 7.7	GERP 2.2, phastCons 1
Overall
CADD	41.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CCNT2
Protein: p.Arg255Ter
Coding: c.763C>T
MANE Select: NM_058241
Type: single nucleotide variant
Location: chr2:134952700 (GRCh38)
Gene constraint: LOEUF 0.428 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 59.93 · 1 PDB
Residue 255: the 'interaction with mdfic and mdfi' region; the 'interaction with polr2a' region; an α-helix

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

Similar variants

CCNT2 p.Arg255Gln Uncertain significance ★ ⚠ same residue
CCNT2 p.Asp717Asn Uncertain significance ★★ ⚠ same type
CCNT2 p.Ala335Ser Uncertain significance ★ ⚠ same type
CCNT2 p.Ala458Thr 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
CCNT2 p.Asp119Glu 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-arg255ter (accessed [today's date]).

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