Is CDC34 p.Ile96= (c.288C>T) pathogenic?

CDC34 p.Ile96= (c.288C>T) is classified Likely benign in CDC34 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-27). Ultra-rare (popmax 0.01%, sas).

How common is CDC34 p.Ile96= (c.288C>T) in the general population?

CDC34 p.Ile96= (c.288C>T) is ultra-rare (popmax 0.01%, sas) (gnomAD).

CDC34 p.Ile96=

c.288C>T · VCV3488348

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.01%, sas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2.2	GERP -4.2
Overall
CADD	2.67	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.01% South Asian · 9/89,998 alleles

Filtering AF 0.00519% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0039%

Overall 0.00405% 65/1,606,622 alleles · ultra-rare exomes 57/1,454,452 · genomes 8/152,170 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.01%	10,000
African / African-American	0.00802%	12,469
European (non-Finnish)	0.00408%	24,530
East Asian	0.00224%	44,610
Remaining individualsnot grpmax-eligible	0.00161%	62,172

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.Ile96=
Coding: c.288C>T
MANE Select: NM_004359
Type: single nucleotide variant
Location: chr19:536266 (GRCh38)
Gene constraint: LOEUF 1.136 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.52 · 5 PDB
Residue 96: the ubc core domain; an α-helix

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.Arg76Gln 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-ile96 (accessed [today's date]).

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