Is CDT1 p.Arg19fs (c.55dup) pathogenic?

CDT1 p.Arg19fs (c.55dup) is classified Pathogenic in CDT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-12). Ultra-rare (popmax 0.0181%, eas).

How common is CDT1 p.Arg19fs (c.55dup) in the general population?

CDT1 p.Arg19fs (c.55dup) is ultra-rare (popmax 0.0181%, eas) (gnomAD).

CDT1 p.Arg19fs

c.55dup · VCV4693314

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0181%, eas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 1 of 10
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.45	GERP -1.8, phastCons 0.001

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0181% East Asian · 6/33,206 alleles

Filtering AF 0.00787% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00534%

Overall 0.00238% 35/1,473,628 alleles · ultra-rare exomes 35/1,323,176 · genomes 0/150,452 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0181%	5,534
Ashkenazi Jewishnot grpmax-eligible	0.00799%	12,516
Admixed American	0.00402%	24,881
South Asian	0.00242%	41,256
European (non-Finnish)	0.00189%	52,848
Remaining individualsnot grpmax-eligible	0.00183%	54,776
African / African-American	0.00147%	68,168

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.Arg19fs
Coding: c.55dup
MANE Select: NM_030928
Type: Duplication
Location: chr16:88803879 (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 19: the 'disordered' region

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

Similar variants

CDT1 p.Arg19His Uncertain significance ★ ⚠ same residue
CDT1 p.Arg19= Likely benign ★ same residue
CDT1 p.Arg469fs Pathogenic ★ same type
CDT1 p.Glu504fs Pathogenic ★ same type
CDT1 p.Ser391fs Pathogenic ★ same type
CDT1 c.228+4_228+5dup Conflicting classifications of pathogenicity ★ same type
CDT1 c.1477+13_1477+34dup Likely benign ★ same type

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-arg19fs (accessed [today's date]).

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