Is CDC123 p.Ser238Arg (c.714T>A) pathogenic?

CDC123 p.Ser238Arg (c.714T>A) is classified Uncertain significance in CDC123 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-26). AlphaMissense: likely pathogenic (0.7527); Very rare (popmax 0.00223%, sas).

How common is CDC123 p.Ser238Arg (c.714T>A) in the general population?

CDC123 p.Ser238Arg (c.714T>A) is very rare (popmax 0.00223%, sas) (gnomAD).

What do computational predictors say about CDC123 p.Ser238Arg (c.714T>A)?

AlphaMissense predicts likely pathogenic (score 0.7527) — an in-silico prediction, not a clinical call.

CDC123 p.Ser238Arg

c.714T>A · VCV3829699

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7527 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, sas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.7527	likely pathogenic
REVEL	0.215	benign-leaning
SaProt	LLR -6.96	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.2	GERP -0.51, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 54 kb · p 0.012 · regional, not allelic
Overall
CADD	18.54	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 0.00223% South Asian · 2/89,576 alleles

Filtering AF 0.000371% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000139%

Overall 0.000124% 2/1,607,952 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.Ser238Arg
Coding: c.714T>A
MANE Select: NM_006023
Type: single nucleotide variant
Location: chr10:12238482 (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-ser238arg (accessed [today's date]).

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