Is CDT1 p.Arg462Trp (c.1384C>T) pathogenic?

CDT1 p.Arg462Trp (c.1384C>T) is classified Uncertain significance in CDT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-05-31). AlphaMissense: likely benign (0.2676); Very rare (popmax 0.00534%, nfe).

How common is CDT1 p.Arg462Trp (c.1384C>T) in the general population?

CDT1 p.Arg462Trp (c.1384C>T) is very rare (popmax 0.00534%, nfe) (gnomAD).

What do computational predictors say about CDT1 p.Arg462Trp (c.1384C>T)?

AlphaMissense predicts likely benign (score 0.2676) — an in-silico prediction, not a clinical call.

CDT1 p.Arg462Trp

c.1384C>T · rs755500544 · VCV1038117

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2676 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00534%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.2676	likely benign
REVEL	0.566	indeterminate
SaProt	LLR -12.46	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 0.23, phastCons 1
Regional constraint	o/e 1.19	unconstrained · MANE · 4,443 bp · p 1.2e-07 · regional, not allelic
Overall
CADD	26.9	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 0.00534% European (non-Finnish) · 63/1,179,972 alleles

Filtering AF 0.00426% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00388%

Overall 0.00459% 74/1,612,644 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0144%	6,940
European (non-Finnish)grpmax	0.00534%	18,730
East Asian	0.00223%	44,902
South Asian	0.0011%	91,090

Remaining individuals 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.Arg462Trp
Coding: c.1384C>T
MANE Select: NM_030928
dbSNP: rs755500544
Type: single nucleotide variant
Location: chr16:88807389 (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 462: a UniProt-annotated variant site (in mgors4); the 'interaction with lrwd1' region

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

Similar variants

CDT1 p.Arg462Gln Pathogenic/Likely pathogenic ★★ ⚠ same residue
CDT1 p.Arg462= Likely benign ★ same residue
CDT1 c.832+1G>A 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
CDT1 p.Ala414Ser 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-arg462trp (accessed [today's date]).

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