Is DDB2 p.Ser396Trp (c.1187C>G) pathogenic?

DDB2 p.Ser396Trp (c.1187C>G) is classified Uncertain significance in DDB2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-17). AlphaMissense: likely pathogenic (0.9351); Absent from gnomAD v4.1.

How common is DDB2 p.Ser396Trp (c.1187C>G) in the general population?

DDB2 p.Ser396Trp (c.1187C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DDB2 p.Ser396Trp (c.1187C>G)?

AlphaMissense predicts likely pathogenic (score 0.9351) — an in-silico prediction, not a clinical call.

DDB2 p.Ser396Trp

c.1187C>G · rs781655324 · VCV2753536

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9351 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9351	likely pathogenic · top 9% in DDB2
REVEL	0.391	indeterminate
SaProt	LLR -14.24	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	Δ0.21	donor gain · deltas
Constraint at this position
Conservation	phyloP 5.9	GERP 1.3, phastCons 1
Regional constraint	o/e 0.78	unconstrained · MANE · 24 kb · p 1.9e-07 · regional, not allelic
Overall
CADD	34.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: DDB2
Protein: p.Ser396Trp
Coding: c.1187C>G
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

Similar variants

DDB2 p.Ser396Ter Pathogenic ★ same residue
DDB2 c.702+1G>T Pathogenic/Likely pathogenic ★★ same type
DDB2 p.Arg192Ter Pathogenic/Likely pathogenic ★★ same type
DDB2 p.Arg273His Pathogenic/Likely pathogenic ★★ ⚠ same type
DDB2 p.Arg355Ter Pathogenic ★★ same type
DDB2 p.Arg332His Uncertain significance ★★ ⚠ same type
DDB2 p.Cys66Gly Uncertain significance ★★ ⚠ same type
DDB2 p.Glu178Ala Uncertain significance ★★ ⚠ same type

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-ser396trp (accessed [today's date]).

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