Is DDB2 p.Ile351= (c.1053T>C) pathogenic?

DDB2 p.Ile351= (c.1053T>C) is classified Conflicting classifications of pathogenicity in DDB2 (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2026-01-24). Rare (popmax 0.544%, mid); Associated with xeroderma pigmentosum.

What condition is associated with DDB2 p.Ile351= (c.1053T>C)?

DDB2 p.Ile351= (c.1053T>C) is associated with xeroderma pigmentosum, xeroderma pigmentosum group E (ClinVar).

How common is DDB2 p.Ile351= (c.1053T>C) in the general population?

DDB2 p.Ile351= (c.1053T>C) is rare (popmax 0.544%, mid) (gnomAD).

How is Xeroderma pigmentosum inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

DDB2 p.Ile351=

c.1053T>C · rs61741581 · VCV777199

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

rare (popmax 0.544%, mid)

Conditions

xeroderma pigmentosum

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 -2.3	GERP -0.3
Overall
CADD	4.283	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.544% Middle Eastern · 33/6,062 alleles

Filtering AF 0.398% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.348%

Overall 0.0364% 587/1,614,074 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.544%	184
Admixed American	0.102%	984
Ashkenazi Jewishnot grpmax-eligible	0.0878%	1,139
Remaining individualsnot grpmax-eligible	0.072%	1,389
European (non-Finnish)	0.0333%	3,002
African / African-American	0.028%	3,573
South Asian	0.00878%	11,385

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: DDB2
Protein: p.Ile351=
Coding: c.1053T>C
MANE Select: NM_000107
dbSNP: rs61741581
Type: single nucleotide variant
Location: chr11:47237866 (GRCh38)
Gene constraint: LOEUF 0.719 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 83.69 · 10 PDB
Residue 351: a β-strand

Full DDB2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

xeroderma pigmentosum — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: xeroderma pigmentosum group E

For Xeroderma pigmentosum (Orphanet):

Inheritance: Autosomal recessive
Onset: All ages
Prevalence: 1-9 / 1 000 000 (United States)

Similar variants

DDB2 c.702+1G>T Pathogenic/Likely pathogenic ★★ same condition
DDB2 p.Arg273His Pathogenic/Likely pathogenic ★★ same condition
DDB2 p.Cys66Gly Uncertain significance ★★ ⚠ same condition
DDB2 p.Glu178Ala Uncertain significance ★★ ⚠ same condition
DDB2 p.Phe94Cys Uncertain significance ★★ ⚠ same condition
DDB2 p.Pro357Leu Uncertain significance ★★ ⚠ same condition
DDB2 p.Ser85Cys Uncertain significance ★★ ⚠ same condition
DDB2 p.Val263Ile Uncertain significance ★★ ⚠ same condition

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/ddb2-p-ile351 (accessed [today's date]).

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