Is DDB2 p.Val275Ile (c.823G>A) pathogenic?

DDB2 p.Val275Ile (c.823G>A) is classified Uncertain significance in DDB2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-04-27). AlphaMissense: likely benign (0.0837); Very rare (popmax 0.00267%, afr); Associated with Inborn genetic diseases.

What condition is associated with DDB2 p.Val275Ile (c.823G>A)?

DDB2 p.Val275Ile (c.823G>A) is associated with Inborn genetic diseases (ClinVar).

How common is DDB2 p.Val275Ile (c.823G>A) in the general population?

DDB2 p.Val275Ile (c.823G>A) is very rare (popmax 0.00267%, afr) (gnomAD).

What do computational predictors say about DDB2 p.Val275Ile (c.823G>A)?

AlphaMissense predicts likely benign (score 0.0837) — an in-silico prediction, not a clinical call.

DDB2 p.Val275Ile

c.823G>A · rs1308275397 · VCV2286365

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0837 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0837	likely benign
REVEL	0.059	moderately benign-leaning
SaProt	LLR -6.11	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.48	donor loss, 1 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP 3.9	GERP 0.022, phastCons 1
Regional constraint	o/e 0.78	unconstrained · MANE · 24 kb · p 1.9e-07 · regional, not allelic
Overall
CADD	15.23	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 0.00267% African / African-American · 2/74,936 alleles

Filtering AF 0.000443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.000124% 2/1,614,082 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.Val275Ile
Coding: c.823G>A
MANE Select: NM_000107
dbSNP: rs1308275397
Type: single nucleotide variant
Location: chr11:47234877 (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

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-val275ile (accessed [today's date]).

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