Is CCNT1 p.Ala397Val (c.1190C>T) pathogenic?

CCNT1 p.Ala397Val (c.1190C>T) is classified Uncertain significance in CCNT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-30). AlphaMissense: ambiguous (0.5538); Very rare (popmax 0.00534%, afr).

How common is CCNT1 p.Ala397Val (c.1190C>T) in the general population?

CCNT1 p.Ala397Val (c.1190C>T) is very rare (popmax 0.00534%, afr) (gnomAD).

What do computational predictors say about CCNT1 p.Ala397Val (c.1190C>T)?

AlphaMissense predicts ambiguous (score 0.5538) — an in-silico prediction, not a clinical call.

CCNT1 p.Ala397Val

c.1190C>T · VCV3487501

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5538 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00534%, afr)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.5538	ambiguous
REVEL	0.19	benign-leaning
SaProt	LLR -10.61	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.7, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 1,399 bp · p 0.67 · regional, not allelic
Overall
CADD	27.3	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

Grpmax group 0.00534% African / African-American · 4/74,918 alleles

Filtering AF 0.00175% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.000248% 4/1,614,068 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.Ala397Val
Coding: c.1190C>T
MANE Select: NM_001240
Type: single nucleotide variant
Location: chr12:48694024 (GRCh38)
Gene constraint: LOEUF 0.31 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 60.32 · 29 PDB

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.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
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-ala397val (accessed [today's date]).

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