Is CCNT1 p.Ser36Pro (c.106T>C) pathogenic?

CCNT1 p.Ser36Pro (c.106T>C) is classified Uncertain significance in CCNT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-12). AlphaMissense: likely pathogenic (0.6612); Rare (popmax 0.165%, mid).

How common is CCNT1 p.Ser36Pro (c.106T>C) in the general population?

CCNT1 p.Ser36Pro (c.106T>C) is rare (popmax 0.165%, mid) (gnomAD).

What do computational predictors say about CCNT1 p.Ser36Pro (c.106T>C)?

AlphaMissense predicts likely pathogenic (score 0.6612) — an in-silico prediction, not a clinical call.

CCNT1 p.Ser36Pro

c.106T>C · rs201190553 · VCV2337524

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6612 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.165%, mid)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.6612	likely pathogenic
REVEL	0.351	indeterminate
SaProt	LLR -14.78	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.2	GERP 1.6, phastCons 1
Regional constraint	o/e 0.51	unconstrained · MANE · 22 kb · p 5.1e-16 · regional, not allelic
Overall
CADD	27.4	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 0.165% Middle Eastern · 10/6,062 alleles

Filtering AF 0.0895% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0681%

Overall 0.00855% 138/1,614,240 alleles · rare exomes 125/1,461,868 · genomes 13/152,372 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.165%	606
Remaining individualsnot grpmax-eligible	0.0128%	7,814
European (non-Finnish)	0.00898%	11,132
Admixed American	0.00833%	12,006
South Asian	0.00659%	15,180
African / African-American	0.004%	25,024

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.Ser36Pro
Coding: c.106T>C
MANE Select: NM_001240
dbSNP: rs201190553
Type: single nucleotide variant
Location: chr12:48716570 (GRCh38)
Gene constraint: LOEUF 0.31 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 60.32 · 29 PDB
Residue 36: 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-ser36pro (accessed [today's date]).

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