Is CDC26 p.Arg29Ser (c.85C>A) pathogenic?

CDC26 p.Arg29Ser (c.85C>A) is classified Uncertain significance in CDC26 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-05). AlphaMissense: likely pathogenic (0.6728); Absent from gnomAD v4.1.

How common is CDC26 p.Arg29Ser (c.85C>A) in the general population?

CDC26 p.Arg29Ser (c.85C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CDC26 p.Arg29Ser (c.85C>A)?

AlphaMissense predicts likely pathogenic (score 0.6728) — an in-silico prediction, not a clinical call.

CDC26 p.Arg29Ser

c.85C>A · VCV4650832

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6728 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6728	likely pathogenic
REVEL	0.285	benign-leaning
SaProt	LLR -6.73	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 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	24.2	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CDC26
Protein: p.Arg29Ser
Coding: c.85C>A
MANE Select: NM_139286
Type: single nucleotide variant
Location: chr9:113267436 (GRCh38)
Gene constraint: LOEUF 1.64 · pLI 0.29 (gnomAD)
Structure: AlphaFold pLDDT 75.13 · 21 PDB

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

Similar variants

CDC26 p.Arg29His Uncertain significance ★ ⚠ same residue
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
CDC26 p.Ser78Cys 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-arg29ser (accessed [today's date]).

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