Is CDC23 p.Val191Ala (c.572T>C) pathogenic?

CDC23 p.Val191Ala (c.572T>C) is classified Uncertain significance in CDC23 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-11). AlphaMissense: likely pathogenic (0.6812); Very rare (popmax 0.00167%, amr).

How common is CDC23 p.Val191Ala (c.572T>C) in the general population?

CDC23 p.Val191Ala (c.572T>C) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about CDC23 p.Val191Ala (c.572T>C)?

AlphaMissense predicts likely pathogenic (score 0.6812) — an in-silico prediction, not a clinical call.

CDC23 p.Val191Ala

c.572T>C · VCV4223198

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6812 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6812	likely pathogenic
REVEL	0.283	benign-leaning
SaProt	LLR -7.21	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · A>C here scores Δ0.31 · evaluated, not missing
Constraint at this position
Conservation	phyloP 11	GERP 1.9, phastCons 1
Regional constraint	o/e 0.75	unconstrained · MANE · 8,181 bp · p 0.00013 · regional, not allelic
Overall
CADD	22.3	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 0.00167% Admixed American · 1/59,998 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000372% 6/1,614,054 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	59,998
Remaining individualsnot grpmax-eligible	0.0016%	62,482
European (non-Finnish)	0.000339%	295,010

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.Val191Ala
Coding: c.572T>C
MANE Select: NM_004661
Type: single nucleotide variant
Location: chr5:138201189 (GRCh38)
Gene constraint: LOEUF 0.452 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 85.74 · 20 PDB
Residue 191: an α-helix

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-val191ala (accessed [today's date]).

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