Is DDB2 p.Thr305= (c.915C>G) pathogenic?

DDB2 p.Thr305= (c.915C>G) is classified Likely benign in DDB2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-02-10). Very rare (popmax 0.000339%, nfe); Associated with xeroderma pigmentosum.

What condition is associated with DDB2 p.Thr305= (c.915C>G)?

DDB2 p.Thr305= (c.915C>G) is associated with xeroderma pigmentosum (ClinVar).

How common is DDB2 p.Thr305= (c.915C>G) in the general population?

DDB2 p.Thr305= (c.915C>G) is very rare (popmax 0.000339%, nfe) (gnomAD).

How is Xeroderma pigmentosum inherited?

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

DDB2 p.Thr305=

c.915C>G · rs758199547 · VCV1692154

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000339%, nfe)

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 -0.4	GERP -3.5, phastCons 0.083
Overall
CADD	6.594	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000339% European (non-Finnish) · 4/1,180,046 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000248% 4/1,614,100 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.Thr305=
Coding: c.915C>G
MANE Select: NM_000107
dbSNP: rs758199547
Type: single nucleotide variant
Location: chr11:47235304 (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 305: 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

For Xeroderma pigmentosum (Orphanet):

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

Similar variants

DDB2 p.Cys66Gly Uncertain significance ★★ ⚠ same condition
DDB2 p.Met215Thr Likely benign ★★ same condition
DDB2 p.Pro290= 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-thr305 (accessed [today's date]).

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