Is DDB2 p.Pro290Leu (c.869C>T) pathogenic?

DDB2 p.Pro290Leu (c.869C>T) is classified Uncertain significance in DDB2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-05-21). AlphaMissense: likely pathogenic (0.606); Very rare (popmax 8.47e-05%, nfe); Associated with xeroderma pigmentosum.

What condition is associated with DDB2 p.Pro290Leu (c.869C>T)?

DDB2 p.Pro290Leu (c.869C>T) is associated with xeroderma pigmentosum (ClinVar).

How common is DDB2 p.Pro290Leu (c.869C>T) in the general population?

DDB2 p.Pro290Leu (c.869C>T) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

How is Xeroderma pigmentosum inherited?

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

What do computational predictors say about DDB2 p.Pro290Leu (c.869C>T)?

AlphaMissense predicts likely pathogenic (score 0.606) — an in-silico prediction, not a clinical call.

DDB2 p.Pro290Leu

c.869C>T · rs2135512289 · VCV1692152

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.606 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

xeroderma pigmentosum

Computational evidence

Protein change
AlphaMissense	0.606	likely pathogenic
REVEL	0.192	benign-leaning
SaProt	LLR -12.36	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.1	GERP 1.2, phastCons 1
Regional constraint	o/e 0.78	unconstrained · MANE · 24 kb · p 1.9e-07 · regional, not allelic
Overall
CADD	26.8	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 8.47e-05% European (non-Finnish) · 1/1,180,036 alleles

Overall 6.84e-05% 1/1,461,868 alleles · very rare

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.Pro290Leu
Coding: c.869C>T
MANE Select: NM_000107
dbSNP: rs2135512289
Type: single nucleotide variant
Location: chr11:47234923 (GRCh38)
Gene constraint: LOEUF 0.719 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 83.69 · 10 PDB

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

For Xeroderma pigmentosum (Orphanet):

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

Similar variants

DDB2 p.Pro290= Likely benign ★★ same residue
DDB2 p.Cys66Gly Uncertain significance ★★ ⚠ same condition
DDB2 p.Met215Thr Likely benign ★★ same condition
DDB2 c.127+5T>G Conflicting classifications of pathogenicity ★ same condition
DDB2 c.264+8A>G Conflicting classifications of pathogenicity ★ same condition
DDB2 c.603-4C>G Uncertain significance ★ same condition
DDB2 c.702+5G>A Uncertain significance ★ same condition
DDB2 p.Ala410Thr Conflicting classifications of pathogenicity ★ ⚠ 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-pro290leu (accessed [today's date]).

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