Is CDT1 p.Arg514Cys (c.1540C>T) pathogenic?

CDT1 p.Arg514Cys (c.1540C>T) is classified Uncertain significance in CDT1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-08-28). AlphaMissense: likely benign (0.0844); Very rare (popmax 0.00237%, nfe); Associated with Inborn genetic diseases.

What condition is associated with CDT1 p.Arg514Cys (c.1540C>T)?

CDT1 p.Arg514Cys (c.1540C>T) is associated with Inborn genetic diseases (ClinVar).

How common is CDT1 p.Arg514Cys (c.1540C>T) in the general population?

CDT1 p.Arg514Cys (c.1540C>T) is very rare (popmax 0.00237%, nfe) (gnomAD).

What do computational predictors say about CDT1 p.Arg514Cys (c.1540C>T)?

AlphaMissense predicts likely benign (score 0.0844) — an in-silico prediction, not a clinical call.

CDT1 p.Arg514Cys

c.1540C>T · rs766544551 · VCV1337775

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0844 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00237%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0844	likely benign
REVEL	0.052	moderately benign-leaning
SaProt	LLR -9.87	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 0.85	GERP 0.36, phastCons 0.013
Regional constraint	o/e 1.19	unconstrained · MANE · 4,443 bp · p 1.2e-07 · regional, not allelic
Overall
CADD	21.6	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 0.00237% European (non-Finnish) · 28/1,179,968 alleles

Filtering AF 0.00164% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00142%

Overall 0.00217% 35/1,612,746 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0032%	31,236
European (non-Finnish)grpmax	0.00237%	42,142
East Asian	0.00223%	44,886
South Asian	0.0022%	45,527
Admixed American	0.00167%	59,982
African / African-American	0.00133%	74,952

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.Arg514Cys
Coding: c.1540C>T
MANE Select: NM_030928
dbSNP: rs766544551
Type: single nucleotide variant
Location: chr16:88808177 (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 514: 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

Similar variants

CDT1 p.Arg514His Conflicting classifications of pathogenicity ★ ⚠ same residue
CDT1 p.Arg514Leu 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-arg514cys (accessed [today's date]).

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