Is DDI2 p.Phe30= (c.90C>T) pathogenic?

DDI2 p.Phe30= (c.90C>T) is classified Uncertain significance in DDI2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-01). Ultra-rare (popmax 0.0703%, amr).

How common is DDI2 p.Phe30= (c.90C>T) in the general population?

DDI2 p.Phe30= (c.90C>T) is ultra-rare (popmax 0.0703%, amr) (gnomAD).

DDI2 p.Phe30=

c.90C>T · rs776279047 · VCV2638293

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0703%, amr)

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 5.7	GERP 1.8, phastCons 1
Overall
CADD	16.44	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0703% Admixed American · 42/59,770 alleles

Filtering AF 0.0534% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0475%

Overall 0.00298% 48/1,610,006 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0703%	1,423
Remaining individualsnot grpmax-eligible	0.00321%	31,185
European (non-Finnish)	0.000339%	294,750

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: DDI2
Protein: p.Phe30=
Coding: c.90C>T
MANE Select: NM_032341
dbSNP: rs776279047
Type: single nucleotide variant
Location: chr1:15617760 (GRCh38)
Gene constraint: LOEUF 0.223 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 79.85 · 3 PDB
Residue 30: the ubiquitin-like domain; an α-helix

Full DDI2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DDI2 p.Ala394Pro Uncertain significance ★ ⚠ same type
DDI2 p.Arg108Gln Uncertain significance ★ ⚠ same type
DDI2 p.Arg108Trp Uncertain significance ★ ⚠ same type
DDI2 p.Arg110His Uncertain significance ★ ⚠ same type
DDI2 p.Arg139Ter Uncertain significance ★ same type
DDI2 p.Arg173Gly Uncertain significance ★ ⚠ same type
DDI2 p.Arg184Gln Uncertain significance ★ ⚠ same type
DDI2 p.Arg277Gln 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/ddi2-p-phe30 (accessed [today's date]).

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