Is CDT1 p.Leu529= (c.1587C>G) pathogenic?

CDT1 p.Leu529= (c.1587C>G) is classified Benign in CDT1 (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-02-04). Common (popmax 70.8%, afr) — too common for a highly-penetrant pathogenic allele; Associated with Meier-Gorlin syndrome 4.

What condition is associated with CDT1 p.Leu529= (c.1587C>G)?

CDT1 p.Leu529= (c.1587C>G) is associated with Meier-Gorlin syndrome 4 (ClinVar).

CDT1 p.Leu529=

Q: How common is CDT1 p.Leu529= (c.1587C>G) in the general population?

CDT1 p.Leu529= (c.1587C>G) is common (popmax 70.8%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1587C>G · rs572275 · VCV128673

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Common

common (popmax 70.8%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

Meier-Gorlin syndrome 4

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 2.2	GERP -3, phastCons 1
Overall
CADD	0.567	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 70.8% African / African-American · 53,085/74,944 alleles

Filtering AF 70.3% ClinGen BA1/BS1 input FAF95, joint · FAF99 70.1%

Overall 38.9% 624,984/1,607,606 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	70.8%	1
East Asian	70.6%	1
Middle Eastern	54.4%	2
Ashkenazi Jewishnot grpmax-eligible	51.9%	2
Admixed American	44.1%	2
Remaining individualsnot grpmax-eligible	42.4%	2
Amishnot grpmax-eligible	41.5%	2
South Asian	39.3%	3
European (non-Finnish)	35%	3
Finnishnot grpmax-eligible	33.6%	3

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.Leu529=
Coding: c.1587C>G
MANE Select: NM_030928
dbSNP: rs572275
Type: single nucleotide variant
Location: chr16:88808224 (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 529: the 'interaction with lrwd1' region

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

Disease context

Meier-Gorlin syndrome 4 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CDT1 c.832+1G>A Pathogenic/Likely pathogenic ★★ same condition
CDT1 p.Arg462Gln Pathogenic/Likely pathogenic ★★ ⚠ same condition
CDT1 p.Arg250Cys Uncertain significance ★★ ⚠ same condition
CDT1 p.Gly281Arg Uncertain significance ★★ ⚠ same condition
CDT1 p.Val204Met Uncertain significance ★★ ⚠ same condition
CDT1 p.Cys234Arg Benign ★★ same condition
CDT1 p.His305= Benign ★★ same condition
CDT1 p.Pro333= Likely benign ★★ 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-leu529 (accessed [today's date]).

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