Is CDC26 p.Ser78Cys (c.233C>G) pathogenic?

CDC26 p.Ser78Cys (c.233C>G) is classified Uncertain significance in CDC26 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-27). AlphaMissense: likely benign (0.0953); Very rare (popmax 0.00824%, nfe).

How common is CDC26 p.Ser78Cys (c.233C>G) in the general population?

CDC26 p.Ser78Cys (c.233C>G) is very rare (popmax 0.00824%, nfe) (gnomAD).

What do computational predictors say about CDC26 p.Ser78Cys (c.233C>G)?

AlphaMissense predicts likely benign (score 0.0953) — an in-silico prediction, not a clinical call.

CDC26 p.Ser78Cys

c.233C>G · VCV4223241

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0953 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00824%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0953	likely benign
REVEL	0.269	benign-leaning
SaProt	LLR -9.11	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 12	GERP 2.5, phastCons 1
Regional constraint	o/e 0.64	unconstrained · MANE · 5,241 bp · p 0.00023 · regional, not allelic
Overall
CADD	26.2	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

Grpmax group 0.00824% European (non-Finnish) · 94/1,141,180 alleles

Filtering AF 0.00687% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00637%

Overall 0.00637% 98/1,538,854 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00824%	12,140
Remaining individualsnot grpmax-eligible	0.00337%	29,679
African / African-American	0.0028%	35,660

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: CDC26
Protein: p.Ser78Cys
Coding: c.233C>G
MANE Select: NM_139286
Type: single nucleotide variant
Location: chr9:113267288 (GRCh38)
Gene constraint: LOEUF 1.64 · pLI 0.29 (gnomAD)
Structure: AlphaFold pLDDT 75.13 · 21 PDB
Residue 78: the 'disordered' region

Full CDC26 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CDC26 p.Arg29His Uncertain significance ★ ⚠ same type
CDC26 p.Arg29Ser Uncertain significance ★ ⚠ same type
CDC26 p.Glu27Gly Uncertain significance ★ ⚠ same type
CDC26 p.Ile16Thr Uncertain significance ★ ⚠ same type
CDC26 p.Ile48Val Uncertain significance ★ ⚠ same type
CDC26 p.Ile61Val Uncertain significance ★ ⚠ same type
CDC26 p.Leu50Phe Uncertain significance ★ ⚠ same type
CDC26 p.Ser52Asn 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/cdc26-p-ser78cys (accessed [today's date]).

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