Is DDB2 p.Ser396Ter (c.1187C>A) pathogenic?

DDB2 p.Ser396Ter (c.1187C>A) is classified Pathogenic in DDB2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-01-03). Very rare (popmax 0.00133%, afr); Associated with xeroderma pigmentosum group E.

What condition is associated with DDB2 p.Ser396Ter (c.1187C>A)?

DDB2 p.Ser396Ter (c.1187C>A) is associated with xeroderma pigmentosum group E (ClinVar).

How common is DDB2 p.Ser396Ter (c.1187C>A) in the general population?

DDB2 p.Ser396Ter (c.1187C>A) is very rare (popmax 0.00133%, afr) (gnomAD).

How is Xeroderma pigmentosum inherited?

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

DDB2 p.Ser396Ter

c.1187C>A · rs781655324 · VCV1333388

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Conditions

xeroderma pigmentosum group E

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 8 of 10
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.21 · evaluated, not missing
Constraint at this position
Conservation	phyloP 5.9	GERP 1.3, phastCons 1
Overall
CADD	41.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00133% African / African-American · 1/74,910 alleles

Overall 0.000124% 2/1,614,008 alleles · very rare exomes 1/1,461,868 · genomes 1/152,140 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00133%	74,910
European (non-Finnish)	8.47e-05%	1,180,032

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.Ser396Ter
Coding: c.1187C>A
MANE Select: NM_000107
dbSNP: rs781655324
Type: single nucleotide variant
Location: chr11:47238000 (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 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 p.Ser396Trp Uncertain significance ★ ⚠ same residue
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

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-ser396ter (accessed [today's date]).

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