Is CDT1 p.Pro471Ala (c.1411C>G) pathogenic?

CDT1 p.Pro471Ala (c.1411C>G) is classified Conflicting classifications of pathogenicity in CDT1 (ClinVar, Conflicting submitters, 9 submitters; last evaluated 2026-01-27). AlphaMissense: likely benign (0.0848); Rare (popmax 0.535%, nfe); Associated with Inborn genetic diseases.

What condition is associated with CDT1 p.Pro471Ala (c.1411C>G)?

CDT1 p.Pro471Ala (c.1411C>G) is associated with Inborn genetic diseases, Meier-Gorlin syndrome 4 (ClinVar).

How common is CDT1 p.Pro471Ala (c.1411C>G) in the general population?

CDT1 p.Pro471Ala (c.1411C>G) is rare (popmax 0.535%, nfe) (gnomAD).

What do computational predictors say about CDT1 p.Pro471Ala (c.1411C>G)?

AlphaMissense predicts likely benign (score 0.0848) — an in-silico prediction, not a clinical call.

CDT1 p.Pro471Ala

c.1411C>G · rs141663679 · VCV210649

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 9 submitters

AlphaMissense

likely benign

0.0848 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.535%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0848	likely benign
REVEL	0.274	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 -1.1, phastCons 1
Regional constraint	o/e 1.19	unconstrained · MANE · 4,443 bp · p 1.2e-07 · regional, not allelic
Overall
CADD	16.61	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 0.535% European (non-Finnish) · 6,309/1,179,986 alleles

Filtering AF 0.524% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.519%

Overall 0.42% 6,769/1,612,986 alleles · rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.535%	187
Remaining individualsnot grpmax-eligible	0.386%	259
Admixed American	0.13%	770
African / African-American	0.0959%	1,043
Middle Eastern	0.0496%	2,015
Finnishnot grpmax-eligible	0.0429%	2,330
South Asian	0.0395%	2,530
Ashkenazi Jewishnot grpmax-eligible	0.0101%	9,866

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.Pro471Ala
Coding: c.1411C>G
MANE Select: NM_030928
dbSNP: rs141663679
Type: single nucleotide variant
Location: chr16:88807416 (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 471: the 'interaction with lrwd1' 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

Also linked: Meier-Gorlin syndrome 4

Similar variants

CDT1 c.832+1G>A Pathogenic/Likely pathogenic ★★ same condition
CDT1 p.Arg462Gln Pathogenic/Likely pathogenic ★★ ⚠ same condition
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.Ala414Ser Uncertain significance ★★ ⚠ same condition
CDT1 p.Ala431Thr 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-pro471ala (accessed [today's date]).

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