Is CDC23 p.Ile503Thr (c.1508T>C) pathogenic?

CDC23 p.Ile503Thr (c.1508T>C) is classified Uncertain significance in CDC23 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-05). AlphaMissense: likely benign (0.0671); Absent from gnomAD v4.1.

How common is CDC23 p.Ile503Thr (c.1508T>C) in the general population?

CDC23 p.Ile503Thr (c.1508T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CDC23 p.Ile503Thr (c.1508T>C)?

AlphaMissense predicts likely benign (score 0.0671) — an in-silico prediction, not a clinical call.

CDC23 p.Ile503Thr

c.1508T>C · rs748041098 · VCV3140795

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0671 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0671	likely benign
REVEL	0.073	moderately benign-leaning
SaProt	LLR -4.56	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 9.4	GERP 1.9, phastCons 1
Regional constraint	o/e 0.52	unconstrained · MANE · 9,396 bp · p 8.3e-19 · regional, not allelic
Overall
CADD	18.99	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CDC23
Protein: p.Ile503Thr
Coding: c.1508T>C
MANE Select: NM_004661
dbSNP: rs748041098
Type: single nucleotide variant
Location: chr5:138189748 (GRCh38)
Gene constraint: LOEUF 0.452 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 85.74 · 20 PDB

Full CDC23 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CDC23 c.1166+2T>G Uncertain significance ★ same type
CDC23 p.Ala68Asp Uncertain significance ★ ⚠ same type
CDC23 p.Arg424Gln Uncertain significance ★ ⚠ same type
CDC23 p.Arg424Trp Uncertain significance ★ ⚠ same type
CDC23 p.Arg585His Uncertain significance ★ ⚠ same type
CDC23 p.Asn110His Uncertain significance ★ ⚠ same type
CDC23 p.Asn23Tyr Uncertain significance ★ ⚠ same type
CDC23 p.Asn287Ser 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/cdc23-p-ile503thr (accessed [today's date]).

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