Is CDC23 p.Leu167Phe (c.499C>T) pathogenic?

CDC23 p.Leu167Phe (c.499C>T) is classified Uncertain significance in CDC23 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-06). AlphaMissense: likely pathogenic (0.9274); Very rare (popmax 0.000678%, nfe).

How common is CDC23 p.Leu167Phe (c.499C>T) in the general population?

CDC23 p.Leu167Phe (c.499C>T) is very rare (popmax 0.000678%, nfe) (gnomAD).

What do computational predictors say about CDC23 p.Leu167Phe (c.499C>T)?

AlphaMissense predicts likely pathogenic (score 0.9274) — an in-silico prediction, not a clinical call.

CDC23 p.Leu167Phe

c.499C>T · rs1486155075 · VCV3140798

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9274 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000678%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9274	likely pathogenic
REVEL	0.157	moderately benign-leaning
SaProt	LLR -10.62	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 10	GERP 1.9, phastCons 1
Regional constraint	o/e 0.75	unconstrained · MANE · 8,181 bp · p 0.00013 · regional, not allelic
Overall
CADD	23.9	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 0.000678% European (non-Finnish) · 8/1,179,924 alleles

Filtering AF 0.000292% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000211%

Overall 0.000547% 8/1,461,724 alleles · very rare

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: CDC23
Protein: p.Leu167Phe
Coding: c.499C>T
MANE Select: NM_004661
dbSNP: rs1486155075
Type: single nucleotide variant
Location: chr5:138201365 (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-leu167phe (accessed [today's date]).

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