Is CCNT1 p.Ala489Val (c.1466C>T) pathogenic?

CCNT1 p.Ala489Val (c.1466C>T) is classified Uncertain significance in CCNT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-19). AlphaMissense: likely benign (0.0803); Rare (popmax 0.301%, afr).

How common is CCNT1 p.Ala489Val (c.1466C>T) in the general population?

CCNT1 p.Ala489Val (c.1466C>T) is rare (popmax 0.301%, afr) (gnomAD).

What do computational predictors say about CCNT1 p.Ala489Val (c.1466C>T)?

AlphaMissense predicts likely benign (score 0.0803) — an in-silico prediction, not a clinical call.

CCNT1 p.Ala489Val

c.1466C>T · VCV4222208

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0803 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.301%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0803	likely benign
REVEL	0.03	moderately benign-leaning
SaProt	LLR -6.97	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.4	GERP 0.67, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 1,399 bp · p 0.67 · regional, not allelic
Overall
CADD	21.8	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 0.301% African / African-American · 226/75,030 alleles

Filtering AF 0.269% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.257%

Overall 0.019% 306/1,614,098 alleles · rare exomes 171/1,461,830 · genomes 135/152,268 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.301%	332
Admixed American	0.0167%	6,001
Middle Eastern	0.0165%	6,062
Remaining individualsnot grpmax-eligible	0.0128%	7,813
European (non-Finnish)	0.00517%	19,345

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.Ala489Val
Coding: c.1466C>T
MANE Select: NM_001240
Type: single nucleotide variant
Location: chr12:48693748 (GRCh38)
Gene constraint: LOEUF 0.31 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 60.32 · 29 PDB
Residue 489: the 'histidine-rich domain (hrd)' region; the 'disordered' region

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.Arg25Gly Uncertain significance ★ ⚠ same type
CCNT1 p.Arg333Cys Uncertain significance ★ ⚠ same type
CCNT1 p.Arg333His Uncertain significance ★ ⚠ same type
CCNT1 p.Arg393His 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-ala489val (accessed [today's date]).

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