Is CDT1 p.Leu423= (c.1267C>T) pathogenic?

CDT1 p.Leu423= (c.1267C>T) is classified Likely benign in CDT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-16). Very rare (popmax 0.00161%, nfe).

How common is CDT1 p.Leu423= (c.1267C>T) in the general population?

CDT1 p.Leu423= (c.1267C>T) is very rare (popmax 0.00161%, nfe) (gnomAD).

CDT1 p.Leu423=

c.1267C>T · rs1172918049 · VCV1092229

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00161%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.81	GERP -1, phastCons 1
Overall
CADD	8.224	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00161% European (non-Finnish) · 19/1,179,786 alleles

Filtering AF 0.00103% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00083%

Overall 0.00124% 20/1,612,272 alleles · very rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,562
European (non-Finnish)grpmax	0.00161%	62,094

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Leu423=
Coding: c.1267C>T
MANE Select: NM_030928
dbSNP: rs1172918049
Type: single nucleotide variant
Location: chr16:88807195 (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 423: 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-leu423 (accessed [today's date]).

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