Is CDT1 p.Arg228Cys (c.682C>T) pathogenic?

CDT1 p.Arg228Cys (c.682C>T) is classified Uncertain significance in CDT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-26). AlphaMissense: likely benign (0.1484); Very rare (popmax 0.00439%, sas); Associated with Inborn genetic diseases.

What condition is associated with CDT1 p.Arg228Cys (c.682C>T)?

CDT1 p.Arg228Cys (c.682C>T) is associated with Inborn genetic diseases (ClinVar).

How common is CDT1 p.Arg228Cys (c.682C>T) in the general population?

CDT1 p.Arg228Cys (c.682C>T) is very rare (popmax 0.00439%, sas) (gnomAD).

What do computational predictors say about CDT1 p.Arg228Cys (c.682C>T)?

AlphaMissense predicts likely benign (score 0.1484) — an in-silico prediction, not a clinical call.

CDT1 p.Arg228Cys

c.682C>T · VCV3999860

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1484 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00439%, sas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1484	likely benign
REVEL	0.361	indeterminate
SaProt	LLR -9.68	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	Δ0.20	donor gain · deltas
Constraint at this position
Conservation	phyloP 4	GERP 0.28, phastCons 1
Regional constraint	o/e 1.19	unconstrained · MANE · 4,443 bp · p 1.2e-07 · regional, not allelic
Overall
CADD	25.2	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00439% South Asian · 4/91,076 alleles

Filtering AF 0.00143% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000891%

Overall 0.000744% 12/1,612,670 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00439%	22,769
African / African-American	0.00266%	37,527
East Asian	0.00223%	44,870
European (non-Finnish)	0.000424%	235,988

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.Arg228Cys
Coding: c.682C>T
MANE Select: NM_030928
Type: single nucleotide variant
Location: chr16:88805633 (GRCh38)
Gene constraint: LOEUF 1.737 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 74.51 · 6 PDB

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

Similar variants

CDT1 p.Arg228His Uncertain significance ★★ ⚠ same residue
CDT1 p.Arg228Leu Uncertain significance ★ ⚠ same residue
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-arg228cys (accessed [today's date]).

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