Is CDT1 p.Arg459= (c.1377C>T) pathogenic?

CDT1 p.Arg459= (c.1377C>T) is classified Benign in CDT1 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-02-04). Common (popmax 10.6%, mid) — too common for a highly-penetrant pathogenic allele.

CDT1 p.Arg459=

Q: How common is CDT1 p.Arg459= (c.1377C>T) in the general population?

CDT1 p.Arg459= (c.1377C>T) is common (popmax 10.6%, mid) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1377C>T · rs3218730 · VCV128669

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Common

common (popmax 10.6%, mid) — too common for a highly-penetrant pathogenic allele

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -9	GERP -2.8
Overall
CADD	1.295	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 10.6% Middle Eastern · 639/6,042 alleles

Filtering AF 9.9% ClinGen BA1/BS1 input FAF95, joint · FAF99 9.63%

Overall 5.45% 87,926/1,612,690 alleles · common

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	13.8%	7
Middle Easterngrpmax	10.6%	9
South Asian	8.22%	12
Remaining individualsnot grpmax-eligible	5.9%	17
African / African-American	5.65%	18
European (non-Finnish)	5.25%	19
Admixed American	4.5%	22
Finnishnot grpmax-eligible	3.52%	28
Amishnot grpmax-eligible	2.63%	38
East Asian	1.91%	52

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Arg459=
Coding: c.1377C>T
MANE Select: NM_030928
dbSNP: rs3218730
Type: single nucleotide variant
Location: chr16:88807382 (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 459: the 'interaction with lrwd1' region

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

Similar variants

CDT1 p.Arg459Cys Uncertain significance ★ ⚠ same residue
CDT1 p.Arg459Pro Uncertain significance ★ ⚠ same residue
CDT1 c.832+1G>A Pathogenic/Likely pathogenic ★★ same type
CDT1 p.Arg462Gln Pathogenic/Likely pathogenic ★★ ⚠ same type
CDT1 p.Ala11Val Uncertain significance ★★ ⚠ same type
CDT1 p.Ala144Ser Uncertain significance ★★ ⚠ same type
CDT1 p.Ala167Thr Uncertain significance ★★ ⚠ same type
CDT1 p.Ala217Val Uncertain significance ★★ ⚠ 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-arg459 (accessed [today's date]).

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