Is DDB2 p.Leu138= (c.414C>G) pathogenic?

DDB2 p.Leu138= (c.414C>G) is classified Uncertain significance in DDB2 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-03-30). Absent from gnomAD v4.1; Associated with xeroderma pigmentosum group E.

What condition is associated with DDB2 p.Leu138= (c.414C>G)?

DDB2 p.Leu138= (c.414C>G) is associated with xeroderma pigmentosum group E (ClinVar).

How common is DDB2 p.Leu138= (c.414C>G) in the general population?

DDB2 p.Leu138= (c.414C>G) is absent from gnomAD v4.1 (gnomAD).

How is Xeroderma pigmentosum inherited?

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

DDB2 p.Leu138=

c.414C>G · rs1953409225 · VCV879678

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

xeroderma pigmentosum group E

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 -0.19	GERP -4.3, phastCons 0.28
Overall
CADD	6.575	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: DDB2
Protein: p.Leu138=
Coding: c.414C>G
MANE Select: NM_000107
dbSNP: rs1953409225
Type: single nucleotide variant
Location: chr11:47217007 (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 138: a β-strand

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

Disease context

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

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.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
DDB2 c.1189-21T>C Benign ★★ 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-leu138 (accessed [today's date]).

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