Is CCNT2 p.Ser435Phe (c.1304C>T) pathogenic?

CCNT2 p.Ser435Phe (c.1304C>T) is classified Uncertain significance in CCNT2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-30). AlphaMissense: likely pathogenic (0.5911); Absent from gnomAD v4.1.

How common is CCNT2 p.Ser435Phe (c.1304C>T) in the general population?

CCNT2 p.Ser435Phe (c.1304C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CCNT2 p.Ser435Phe (c.1304C>T)?

AlphaMissense predicts likely pathogenic (score 0.5911) — an in-silico prediction, not a clinical call.

CCNT2 p.Ser435Phe

c.1304C>T · rs2467614838 · VCV3140019

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5911 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.5911	likely pathogenic
REVEL	0.283	benign-leaning
SaProt	LLR -12.31	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 1,371 bp · p 0.29 · regional, not allelic
Overall
CADD	27.0	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

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.Ser435Phe
Coding: c.1304C>T
MANE Select: NM_058241
dbSNP: rs2467614838
Type: single nucleotide variant
Location: chr2:134953759 (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-ser435phe (accessed [today's date]).

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