Is CDT1 p.Ala414Ser (c.1240G>T) pathogenic?

CDT1 p.Ala414Ser (c.1240G>T) is classified Uncertain significance in CDT1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-11-05). AlphaMissense: likely benign (0.1039); Ultra-rare (popmax 0.049%, eas); Associated with Inborn genetic diseases.

What condition is associated with CDT1 p.Ala414Ser (c.1240G>T)?

CDT1 p.Ala414Ser (c.1240G>T) is associated with Inborn genetic diseases (ClinVar).

How common is CDT1 p.Ala414Ser (c.1240G>T) in the general population?

CDT1 p.Ala414Ser (c.1240G>T) is ultra-rare (popmax 0.049%, eas) (gnomAD).

What do computational predictors say about CDT1 p.Ala414Ser (c.1240G>T)?

AlphaMissense predicts likely benign (score 0.1039) — an in-silico prediction, not a clinical call.

CDT1 p.Ala414Ser

c.1240G>T · rs763233317 · VCV1045064

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1039 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.049%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1039	likely benign
REVEL	0.155	moderately benign-leaning
SaProt	LLR -6.93	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 3.1	GERP 0.078, phastCons 0.29
Regional constraint	o/e 1.19	unconstrained · MANE · 4,443 bp · p 1.2e-07 · regional, not allelic
Overall
CADD	14.69	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 0.049% East Asian · 22/44,870 alleles

Filtering AF 0.0332% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0279%

Overall 0.00143% 23/1,612,512 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.049%	2,040
South Asian	0.0011%	91,054

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.Ala414Ser
Coding: c.1240G>T
MANE Select: NM_030928
dbSNP: rs763233317
Type: single nucleotide variant
Location: chr16:88807168 (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 414: the 'disordered' region

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CDT1 p.Ala11Val Uncertain significance ★★ ⚠ same condition
CDT1 p.Ala144Ser Uncertain significance ★★ ⚠ same condition
CDT1 p.Ala167Thr Uncertain significance ★★ ⚠ same condition
CDT1 p.Ala217Val Uncertain significance ★★ ⚠ same condition
CDT1 p.Ala431Thr Uncertain significance ★★ ⚠ same condition
CDT1 p.Ala534Val Uncertain significance ★★ ⚠ same condition
CDT1 p.Ala90Thr Uncertain significance ★★ ⚠ same condition
CDT1 p.Arg131Trp Uncertain significance ★★ ⚠ same condition

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-ala414ser (accessed [today's date]).

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