Is CDC34 p.Arg76Gln (c.227G>A) pathogenic?

CDC34 p.Arg76Gln (c.227G>A) is classified Uncertain significance in CDC34 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-13). AlphaMissense: likely benign (0.2117); Very rare (popmax 0.00653%, nfe).

How common is CDC34 p.Arg76Gln (c.227G>A) in the general population?

CDC34 p.Arg76Gln (c.227G>A) is very rare (popmax 0.00653%, nfe) (gnomAD).

What do computational predictors say about CDC34 p.Arg76Gln (c.227G>A)?

AlphaMissense predicts likely benign (score 0.2117) — an in-silico prediction, not a clinical call.

CDC34 p.Arg76Gln

c.227G>A · VCV3998494

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2117 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00653%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2117	likely benign
REVEL	0.28	benign-leaning
SaProt	LLR -11.84	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.1, phastCons 1
Regional constraint	o/e 0.84	unconstrained · MANE · 9,617 bp · p 0.0029 · regional, not allelic
Overall
CADD	32.0	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 0.00653% European (non-Finnish) · 77/1,179,998 alleles

Filtering AF 0.0053% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0049%

Overall 0.00489% 79/1,613,976 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00653%	15,325
East Asian	0.00223%	44,882
Remaining individualsnot grpmax-eligible	0.0016%	62,502

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: CDC34
Protein: p.Arg76Gln
Coding: c.227G>A
MANE Select: NM_004359
Type: single nucleotide variant
Location: chr19:535886 (GRCh38)
Gene constraint: LOEUF 1.136 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.52 · 5 PDB
Residue 76: the ubc core domain; a β-strand

Full CDC34 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CDC34 p.Ala176Val Uncertain significance ★ ⚠ same type
CDC34 p.Ala196Val Uncertain significance ★ ⚠ same type
CDC34 p.Ala2Ser Uncertain significance ★ ⚠ same type
CDC34 p.Ala44Val Uncertain significance ★ ⚠ same type
CDC34 p.Arg159Gln Uncertain significance ★ ⚠ same type
CDC34 p.Arg3Gln Uncertain significance ★ ⚠ same type
CDC34 p.Arg61Cys Uncertain significance ★ ⚠ same type
CDC34 p.Asp200Asn 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/cdc34-p-arg76gln (accessed [today's date]).

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