Is CDT1 p.Pro412Thr (c.1234C>A) pathogenic?

CDT1 p.Pro412Thr (c.1234C>A) is classified Conflicting classifications of pathogenicity in CDT1 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2026-02-21). AlphaMissense: likely benign (0.07); Ultra-rare (popmax 0.0275%, sas); Associated with Meier-Gorlin syndrome 4.

What condition is associated with CDT1 p.Pro412Thr (c.1234C>A)?

CDT1 p.Pro412Thr (c.1234C>A) is associated with Meier-Gorlin syndrome 4 (ClinVar).

How common is CDT1 p.Pro412Thr (c.1234C>A) in the general population?

CDT1 p.Pro412Thr (c.1234C>A) is ultra-rare (popmax 0.0275%, sas) (gnomAD).

What do computational predictors say about CDT1 p.Pro412Thr (c.1234C>A)?

AlphaMissense predicts likely benign (score 0.07) — an in-silico prediction, not a clinical call.

CDT1 p.Pro412Thr

c.1234C>A · rs770232566 · VCV1495760

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.07 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0275%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Meier-Gorlin syndrome 4

Computational evidence

Protein change
AlphaMissense	0.07	likely benign
REVEL	0.182	moderately benign-leaning
SaProt	LLR -7.68	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 -0.001	GERP -0.21
Regional constraint	o/e 1.19	unconstrained · MANE · 4,443 bp · p 1.2e-07 · regional, not allelic
Overall
CADD	11.91	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 0.0275% South Asian · 25/91,046 alleles

Filtering AF 0.019% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0163%

Overall 0.00178% 26/1,460,202 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0275%	3,642
Middle Eastern	0.0165%	6,060

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.Pro412Thr
Coding: c.1234C>A
MANE Select: NM_030928
dbSNP: rs770232566
Type: single nucleotide variant
Location: chr16:88807162 (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 412: the 'disordered' 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.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-pro412thr (accessed [today's date]).

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