Is CDT1 p.Pro54Ser (c.160C>T) pathogenic?

CDT1 p.Pro54Ser (c.160C>T) is classified Uncertain significance in CDT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-19). AlphaMissense: likely benign (0.0697); Ultra-rare (popmax 0.0242%, mid).

How common is CDT1 p.Pro54Ser (c.160C>T) in the general population?

CDT1 p.Pro54Ser (c.160C>T) is ultra-rare (popmax 0.0242%, mid) (gnomAD).

What do computational predictors say about CDT1 p.Pro54Ser (c.160C>T)?

AlphaMissense predicts likely benign (score 0.0697) — an in-silico prediction, not a clinical call.

CDT1 p.Pro54Ser

c.160C>T · rs2508193297 · VCV1944975

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0697 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0242%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0697	likely benign
REVEL	0.049	moderately benign-leaning
SaProt	LLR -6.44	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 -2.7	GERP -1.9
Regional constraint	o/e 1.19	unconstrained · MANE · 4,443 bp · p 1.2e-07 · regional, not allelic
Overall
CADD	1.699	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 0.0242% Middle Eastern · 1/4,128 alleles

Overall 6.9e-05% 1/1,448,498 alleles · ultra-rare exomes 1/1,296,626 · genomes 0/151,872 · joint denominator

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: CDT1
Protein: p.Pro54Ser
Coding: c.160C>T
MANE Select: NM_030928
dbSNP: rs2508193297
Type: single nucleotide variant
Location: chr16:88803991 (GRCh38)
Gene constraint: LOEUF 1.737 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 74.51 · 6 PDB
Residue 54: the 'disordered' region

Full CDT1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CDT1 p.Pro54= Likely benign ★ same residue
CDT1 c.832+1G>A Pathogenic/Likely pathogenic ★★ same type
CDT1 p.Arg462Gln Pathogenic/Likely pathogenic ★★ ⚠ same type
CDT1 p.Ala11Val Uncertain significance ★★ ⚠ same type
CDT1 p.Ala144Ser Uncertain significance ★★ ⚠ same type
CDT1 p.Ala167Thr Uncertain significance ★★ ⚠ same type
CDT1 p.Ala217Val Uncertain significance ★★ ⚠ same type
CDT1 p.Ala414Ser 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/cdt1-p-pro54ser (accessed [today's date]).

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