Is CDT1 p.Thr262Ala (c.784A>G) pathogenic?

CDT1 p.Thr262Ala (c.784A>G) is classified Benign in CDT1 (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-02-04). AlphaMissense: likely benign (0.0623); Common (popmax 73.3%, eas) — too common for a highly-penetrant pathogenic allele; Associated with Meier-Gorlin syndrome 4.

What condition is associated with CDT1 p.Thr262Ala (c.784A>G)?

CDT1 p.Thr262Ala (c.784A>G) is associated with Meier-Gorlin syndrome 4 (ClinVar).

What do computational predictors say about CDT1 p.Thr262Ala (c.784A>G)?

AlphaMissense predicts likely benign (score 0.0623) — an in-silico prediction, not a clinical call.

CDT1 p.Thr262Ala

Q: How common is CDT1 p.Thr262Ala (c.784A>G) in the general population?

CDT1 p.Thr262Ala (c.784A>G) is common (popmax 73.3%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.784A>G · rs480727 · VCV128682

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

AlphaMissense

likely benign

0.0623 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 73.3%, eas) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Meier-Gorlin syndrome 4

Computational evidence

Protein change
AlphaMissense	0.0623	likely benign
REVEL	0.006	strongly benign-leaning
SaProt	LLR -7.04	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 -3.8	GERP -2.9
Regional constraint	o/e 1.19	unconstrained · MANE · 4,443 bp · p 1.2e-07 · regional, not allelic
Overall
CADD	0.691	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 73.3% East Asian · 32,875/44,846 alleles

Filtering AF 72.6% ClinGen BA1/BS1 input FAF95, joint · FAF99 72.4%

Overall 40.4% 651,550/1,612,382 alleles · common

Ancestry group	Frequency	1 in
East Asiangrpmax	73.3%	1
African / African-American	71.4%	1
Middle Eastern	55.7%	2
Ashkenazi Jewishnot grpmax-eligible	52.4%	2
Amishnot grpmax-eligible	49.2%	2
Admixed American	45.2%	2
Remaining individualsnot grpmax-eligible	44.1%	2
South Asian	41.7%	2
European (non-Finnish)	36.6%	3
Finnishnot grpmax-eligible	34.2%	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.Thr262Ala
Coding: c.784A>G
MANE Select: NM_030928
dbSNP: rs480727
Type: single nucleotide variant
Location: chr16:88805821 (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 262: a UniProt-annotated variant site (in)

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.Leu529= 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-thr262ala (accessed [today's date]).

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