Is CDC26 p.Thr7Arg (c.20C>G) pathogenic?

CDC26 p.Thr7Arg (c.20C>G) is classified Uncertain significance in CDC26 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-12). AlphaMissense: likely pathogenic (0.9896); Very rare (popmax 0.00017%, nfe).

How common is CDC26 p.Thr7Arg (c.20C>G) in the general population?

CDC26 p.Thr7Arg (c.20C>G) is very rare (popmax 0.00017%, nfe) (gnomAD).

What do computational predictors say about CDC26 p.Thr7Arg (c.20C>G)?

AlphaMissense predicts likely pathogenic (score 0.9896) — an in-silico prediction, not a clinical call.

CDC26 p.Thr7Arg

c.20C>G · VCV3998492

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9896 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00017%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9896	likely pathogenic · top 9% in CDC26
REVEL	0.636	indeterminate
SaProt	LLR -15.59	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.2, phastCons 1
Regional constraint	o/e 0.64	unconstrained · MANE · 5,241 bp · p 0.00023 · regional, not allelic
Overall
CADD	24.7	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.00017% European (non-Finnish) · 2/1,178,876 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000124% 2/1,612,568 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: CDC26
Protein: p.Thr7Arg
Coding: c.20C>G
MANE Select: NM_139286
Type: single nucleotide variant
Location: chr9:113272488 (GRCh38)
Gene constraint: LOEUF 1.64 · pLI 0.29 (gnomAD)
Structure: AlphaFold pLDDT 75.13 · 21 PDB
Residue 7: an α-helix

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-thr7arg (accessed [today's date]).

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