Is CCNT1 p.Ile150Phe (c.448A>T) pathogenic?

CCNT1 p.Ile150Phe (c.448A>T) is classified Uncertain significance in CCNT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-04). AlphaMissense: likely pathogenic (0.9782); Very rare (popmax 0.00339%, amr).

How common is CCNT1 p.Ile150Phe (c.448A>T) in the general population?

CCNT1 p.Ile150Phe (c.448A>T) is very rare (popmax 0.00339%, amr) (gnomAD).

What do computational predictors say about CCNT1 p.Ile150Phe (c.448A>T)?

AlphaMissense predicts likely pathogenic (score 0.9782) — an in-silico prediction, not a clinical call.

CCNT1 p.Ile150Phe

c.448A>T · VCV4222204

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9782 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00339%, amr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9782	likely pathogenic · top 5% in CCNT1
REVEL	0.65	pathogenic-leaning
SaProt	LLR -12.07	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 1.8, phastCons 1
Regional constraint	o/e 0.51	unconstrained · MANE · 22 kb · p 5.1e-16 · regional, not allelic
Overall
CADD	27.8	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00339% Admixed American · 2/59,058 alleles

Filtering AF 0.000562% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00021%

Overall 0.000138% 2/1,453,298 alleles · very rare

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: CCNT1
Protein: p.Ile150Phe
Coding: c.448A>T
MANE Select: NM_001240
Type: single nucleotide variant
Location: chr12:48699826 (GRCh38)
Gene constraint: LOEUF 0.31 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 60.32 · 29 PDB
Residue 150: an α-helix

Full CCNT1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCNT1 p.Ala356Glu Uncertain significance ★ ⚠ same type
CCNT1 p.Ala394Thr Uncertain significance ★ ⚠ same type
CCNT1 p.Ala394Val Uncertain significance ★ ⚠ same type
CCNT1 p.Ala397Val Uncertain significance ★ ⚠ same type
CCNT1 p.Ala489Val Uncertain significance ★ ⚠ same type
CCNT1 p.Arg25Gly Uncertain significance ★ ⚠ same type
CCNT1 p.Arg333Cys Uncertain significance ★ ⚠ same type
CCNT1 p.Arg333His 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/ccnt1-p-ile150phe (accessed [today's date]).

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