Is DDB2 p.Gln171Glu (c.511C>G) pathogenic?

DDB2 p.Gln171Glu (c.511C>G) is classified Conflicting classifications of pathogenicity in DDB2 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2026-01-11). AlphaMissense: likely benign (0.0784); Rare (popmax 0.398%, amr); Associated with xeroderma pigmentosum group E.

What condition is associated with DDB2 p.Gln171Glu (c.511C>G)?

DDB2 p.Gln171Glu (c.511C>G) is associated with xeroderma pigmentosum group E (ClinVar).

How common is DDB2 p.Gln171Glu (c.511C>G) in the general population?

DDB2 p.Gln171Glu (c.511C>G) is rare (popmax 0.398%, amr) (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.Gln171Glu (c.511C>G)?

AlphaMissense predicts likely benign (score 0.0784) — an in-silico prediction, not a clinical call.

DDB2 p.Gln171Glu

c.511C>G · rs201703288 · VCV771441

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0784 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.398%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

xeroderma pigmentosum group E

Computational evidence

Protein change
AlphaMissense	0.0784	likely benign
REVEL	0.27	benign-leaning
SaProt	LLR -4.95	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 2.4, phastCons 1
Regional constraint	o/e 0.78	unconstrained · MANE · 24 kb · p 1.9e-07 · regional, not allelic
Overall
CADD	23.1	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 0.398% Admixed American · 239/60,022 alleles

Filtering AF 0.357% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.341%

Overall 0.0149% 240/1,614,072 alleles · rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.398%	251
Remaining individualsnot grpmax-eligible	0.0016%	62,502

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.Gln171Glu
Coding: c.511C>G
MANE Select: NM_000107
dbSNP: rs201703288
Type: single nucleotide variant
Location: chr11:47232868 (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 171: 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-gln171glu (accessed [today's date]).

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