Is DDB2 p.Gln265Arg (c.794A>G) pathogenic?

DDB2 p.Gln265Arg (c.794A>G) is classified Uncertain significance in DDB2 (ClinVar, No assertion criteria, 1 submitter). AlphaMissense: likely benign (0.1218); Very rare (popmax 8.47e-05%, nfe).

How common is DDB2 p.Gln265Arg (c.794A>G) in the general population?

DDB2 p.Gln265Arg (c.794A>G) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about DDB2 p.Gln265Arg (c.794A>G)?

AlphaMissense predicts likely benign (score 0.1218) — an in-silico prediction, not a clinical call.

DDB2 p.Gln265Arg

c.794A>G · rs1953701307 · VCV1050710

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1218 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1218	likely benign
REVEL	0.138	moderately benign-leaning
SaProt	LLR -7.25	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 8.1	GERP 1.3, phastCons 1
Regional constraint	o/e 0.78	unconstrained · MANE · 24 kb · p 1.9e-07 · regional, not allelic
Overall
CADD	21.8	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 8.47e-05% European (non-Finnish) · 1/1,180,014 alleles

Overall 6.84e-05% 1/1,461,880 alleles · very rare

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.Gln265Arg
Coding: c.794A>G
MANE Select: NM_000107
dbSNP: rs1953701307
Type: single nucleotide variant
Location: chr11:47234848 (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 265: a turn

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

Similar variants

DDB2 p.Gln265Lys Uncertain significance ★ ⚠ 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-gln265arg (accessed [today's date]).

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