Is DDB2 p.Asp231Glu (c.693C>G) pathogenic?

DDB2 p.Asp231Glu (c.693C>G) is classified Uncertain significance in DDB2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-15). AlphaMissense: likely benign (0.1326); Very rare (popmax 0.00398%, nfe); Associated with Inborn genetic diseases.

What condition is associated with DDB2 p.Asp231Glu (c.693C>G)?

DDB2 p.Asp231Glu (c.693C>G) is associated with Inborn genetic diseases (ClinVar).

How common is DDB2 p.Asp231Glu (c.693C>G) in the general population?

DDB2 p.Asp231Glu (c.693C>G) is very rare (popmax 0.00398%, nfe) (gnomAD).

What do computational predictors say about DDB2 p.Asp231Glu (c.693C>G)?

AlphaMissense predicts likely benign (score 0.1326) — an in-silico prediction, not a clinical call.

DDB2 p.Asp231Glu

c.693C>G · VCV3271184

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1326 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00398%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1326	likely benign
REVEL	0.06	moderately benign-leaning
SaProt	LLR -5.61	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 -9.3	GERP -4.6
Regional constraint	o/e 0.78	unconstrained · MANE · 24 kb · p 1.9e-07 · regional, not allelic
Overall
CADD	0.29	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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

Grpmax group 0.00398% European (non-Finnish) · 47/1,180,016 alleles

Filtering AF 0.00307% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00275%

Overall 0.00304% 49/1,613,994 alleles · very rare exomes 47/1,461,872 · genomes 2/152,122 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00398%	25,107
Remaining individualsnot grpmax-eligible	0.0016%	62,482
African / African-American	0.00134%	74,904

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.Asp231Glu
Coding: c.693C>G
MANE Select: NM_000107
Type: single nucleotide variant
Location: chr11:47234663 (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 231: a β-strand

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

Similar variants

DDB2 p.Glu178Ala Uncertain significance ★★ ⚠ same condition
DDB2 p.Phe94Cys Uncertain significance ★★ ⚠ same condition
DDB2 p.Pro27Thr Uncertain significance ★★ ⚠ same condition
DDB2 p.Ser85Cys Uncertain significance ★★ ⚠ same condition
DDB2 p.Ser85Tyr Uncertain significance ★★ ⚠ same condition
DDB2 p.Thr406Met Uncertain significance ★★ ⚠ same condition
DDB2 p.Ala301Val Uncertain significance ★ ⚠ same condition
DDB2 p.Arg192Gln 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-asp231glu (accessed [today's date]).

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