Is DDB2 p.Val193Ile (c.577G>A) pathogenic?

DDB2 p.Val193Ile (c.577G>A) is classified Benign/Likely benign in DDB2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-22). AlphaMissense: likely benign (0.078); Rare (popmax 0.391%, sas); Associated with xeroderma pigmentosum group E.

What condition is associated with DDB2 p.Val193Ile (c.577G>A)?

DDB2 p.Val193Ile (c.577G>A) is associated with xeroderma pigmentosum group E (ClinVar).

How common is DDB2 p.Val193Ile (c.577G>A) in the general population?

DDB2 p.Val193Ile (c.577G>A) is rare (popmax 0.391%, sas) (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.Val193Ile (c.577G>A)?

AlphaMissense predicts likely benign (score 0.078) — an in-silico prediction, not a clinical call.

DDB2 p.Val193Ile

c.577G>A · rs200406558 · VCV304917

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.078 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.391%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

xeroderma pigmentosum group E

Computational evidence

Protein change
AlphaMissense	0.078	likely benign
REVEL	0.084	moderately benign-leaning
SaProt	LLR -7.31	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 6.5	GERP 1.3, phastCons 1
Regional constraint	o/e 0.78	unconstrained · MANE · 24 kb · p 1.9e-07 · regional, not allelic
Overall
CADD	18.55	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 0.391% South Asian · 356/91,084 alleles

Filtering AF 0.357% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.344%

Overall 0.0237% 382/1,614,194 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.391%	256
Remaining individualsnot grpmax-eligible	0.0336%	2,977
European (non-Finnish)	0.000424%	236,008

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.Val193Ile
Coding: c.577G>A
MANE Select: NM_000107
dbSNP: rs200406558
Type: single nucleotide variant
Location: chr11:47232934 (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 193: 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-val193ile (accessed [today's date]).

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