Is DDB2 p.Arg20Lys (c.59G>A) pathogenic?

DDB2 p.Arg20Lys (c.59G>A) is classified Conflicting classifications of pathogenicity in DDB2 (ClinVar, Conflicting submitters, 7 submitters; last evaluated 2024-01-02). AlphaMissense: likely benign (0.0735); Ultra-rare (popmax 0.0239%, nfe); Associated with Inborn genetic diseases.

What condition is associated with DDB2 p.Arg20Lys (c.59G>A)?

DDB2 p.Arg20Lys (c.59G>A) is associated with Inborn genetic diseases, xeroderma pigmentosum group E, xeroderma pigmentosum (ClinVar).

How common is DDB2 p.Arg20Lys (c.59G>A) in the general population?

DDB2 p.Arg20Lys (c.59G>A) is ultra-rare (popmax 0.0239%, nfe) (gnomAD).

What do computational predictors say about DDB2 p.Arg20Lys (c.59G>A)?

AlphaMissense predicts likely benign (score 0.0735) — an in-silico prediction, not a clinical call.

DDB2 p.Arg20Lys

c.59G>A · rs373622283 · VCV878228

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 7 submitters

AlphaMissense

likely benign

0.0735 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0239%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0735	likely benign
REVEL	0.15	moderately benign-leaning
SaProt	LLR -8.03	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 0.016	GERP -4.9
Regional constraint	o/e 0.78	unconstrained · MANE · 24 kb · p 1.9e-07 · regional, not allelic
Overall
CADD	7.789	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 0.0239% European (non-Finnish) · 282/1,180,026 alleles

Filtering AF 0.0216% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0206%

Overall 0.0183% 295/1,613,942 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0239%	4,184
Middle Eastern	0.0164%	6,084
Remaining individualsnot grpmax-eligible	0.008%	12,498
African / African-American	0.00534%	18,723
Admixed American	0.005%	19,987

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.Arg20Lys
Coding: c.59G>A
dbSNP: rs373622283
Type: single nucleotide variant
Location: chr11:47215195 (GRCh38)

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: xeroderma pigmentosum group E xeroderma pigmentosum

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-arg20lys (accessed [today's date]).

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