Is CDT1 p.Gln434Pro (c.1301A>C) pathogenic?

CDT1 p.Gln434Pro (c.1301A>C) is classified Uncertain significance in CDT1 (ClinVar, No assertion criteria, 2 submitters). AlphaMissense: ambiguous (0.3755); Rare (popmax 0.141%, sas).

How common is CDT1 p.Gln434Pro (c.1301A>C) in the general population?

CDT1 p.Gln434Pro (c.1301A>C) is rare (popmax 0.141%, sas) (gnomAD).

What do computational predictors say about CDT1 p.Gln434Pro (c.1301A>C)?

AlphaMissense predicts ambiguous (score 0.3755) — an in-silico prediction, not a clinical call.

CDT1 p.Gln434Pro

c.1301A>C · rs555260168 · VCV1206394

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.3755 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.141%, sas)

Computational evidence

Protein change
AlphaMissense	0.3755	ambiguous
REVEL	0.334	indeterminate
SaProt	LLR -10.38	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.4, phastCons 1
Regional constraint	o/e 1.19	unconstrained · MANE · 4,443 bp · p 1.2e-07 · regional, not allelic
Overall
CADD	24.5	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 0.141% South Asian · 128/91,090 alleles

Filtering AF 0.121% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.113%

Overall 0.00819% 132/1,612,486 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.141%	712
Remaining individualsnot grpmax-eligible	0.0048%	20,829
European (non-Finnish)	8.48e-05%	1,179,933

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.Gln434Pro
Coding: c.1301A>C
MANE Select: NM_030928
dbSNP: rs555260168
Type: single nucleotide variant
Location: chr16:88807306 (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 434: an α-helix

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

Similar variants

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
CDT1 p.Ala431Thr 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-gln434pro (accessed [today's date]).

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