Is CDC123 p.Pro31Ser (c.91C>T) pathogenic?

CDC123 p.Pro31Ser (c.91C>T) is classified Uncertain significance in CDC123 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-10). AlphaMissense: ambiguous (0.555); Very rare (popmax 0.000345%, nfe).

How common is CDC123 p.Pro31Ser (c.91C>T) in the general population?

CDC123 p.Pro31Ser (c.91C>T) is very rare (popmax 0.000345%, nfe) (gnomAD).

What do computational predictors say about CDC123 p.Pro31Ser (c.91C>T)?

AlphaMissense predicts ambiguous (score 0.555) — an in-silico prediction, not a clinical call.

CDC123 p.Pro31Ser

c.91C>T · rs1353855260 · VCV2327504

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.555 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000345%, nfe)

Computational evidence

Protein change
AlphaMissense	0.555	ambiguous
REVEL	0.405	indeterminate
SaProt	LLR -12.35	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.9, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 54 kb · p 0.012 · regional, not allelic
Overall
CADD	28.8	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 0.000345% European (non-Finnish) · 4/1,159,562 alleles

Filtering AF 8.1e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.5e-05%

Overall 0.000279% 4/1,432,842 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: CDC123
Protein: p.Pro31Ser
Coding: c.91C>T
MANE Select: NM_006023
dbSNP: rs1353855260
Type: single nucleotide variant
Location: chr10:12198721 (GRCh38)
Gene constraint: LOEUF 1.013 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.82 · 2 PDB

Full CDC123 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CDC123 c.489+3A>C Benign ★★ same type
CDC123 c.847-4A>G Benign ★★ same type
CDC123 p.Ala113Val Uncertain significance ★ ⚠ same type
CDC123 p.Ala279Thr Uncertain significance ★ ⚠ same type
CDC123 p.Ala319Thr Uncertain significance ★ ⚠ same type
CDC123 p.Arg142Gly Uncertain significance ★ ⚠ same type
CDC123 p.Arg142His Uncertain significance ★ ⚠ same type
CDC123 p.Arg167Gln 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/cdc123-p-pro31ser (accessed [today's date]).

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