Is CDT1 p.Arg250His (c.749G>A) pathogenic?

CDT1 p.Arg250His (c.749G>A) is classified Uncertain significance in CDT1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-12-05). AlphaMissense: likely benign (0.1104); Very rare (popmax 0.00446%, eas); Associated with Inborn genetic diseases.

What condition is associated with CDT1 p.Arg250His (c.749G>A)?

CDT1 p.Arg250His (c.749G>A) is associated with Inborn genetic diseases (ClinVar).

How common is CDT1 p.Arg250His (c.749G>A) in the general population?

CDT1 p.Arg250His (c.749G>A) is very rare (popmax 0.00446%, eas) (gnomAD).

What do computational predictors say about CDT1 p.Arg250His (c.749G>A)?

AlphaMissense predicts likely benign (score 0.1104) — an in-silico prediction, not a clinical call.

CDT1 p.Arg250His

c.749G>A · rs774484812 · VCV1431585

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1104 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00446%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1104	likely benign
REVEL	0.288	benign-leaning
SaProt	LLR -9.32	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.38 · evaluated, not missing
Constraint at this position
Conservation	phyloP 12	GERP 0.26, phastCons 1
Regional constraint	o/e 1.19	unconstrained · MANE · 4,443 bp · p 1.2e-07 · regional, not allelic
Overall
CADD	27.6	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 0.00446% East Asian · 2/44,890 alleles

Filtering AF 0.000739% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000276%

Overall 0.000744% 12/1,612,994 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00446%	22,445
Admixed American	0.00333%	30,001
African / African-American	0.00267%	37,465
Remaining individualsnot grpmax-eligible	0.0016%	62,464
European (non-Finnish)	0.000424%	235,995

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.Arg250His
Coding: c.749G>A
MANE Select: NM_030928
dbSNP: rs774484812
Type: single nucleotide variant
Location: chr16:88805786 (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 250: a β-strand

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.Arg250Cys 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
CDT1 p.Ala534Val 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-arg250his (accessed [today's date]).

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