Is DDB1 p.Phe429Val (c.1285T>G) pathogenic?

DDB1 p.Phe429Val (c.1285T>G) is classified Pathogenic in DDB1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2021-07-20). AlphaMissense: likely pathogenic (0.9906); Absent from gnomAD v4.1; Associated with White-Kernohan syndrome.

What condition is associated with DDB1 p.Phe429Val (c.1285T>G)?

DDB1 p.Phe429Val (c.1285T>G) is associated with White-Kernohan syndrome (ClinVar).

How common is DDB1 p.Phe429Val (c.1285T>G) in the general population?

DDB1 p.Phe429Val (c.1285T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DDB1 p.Phe429Val (c.1285T>G)?

AlphaMissense predicts likely pathogenic (score 0.9906) — an in-silico prediction, not a clinical call.

DDB1 p.Phe429Val

c.1285T>G · rs2134916397 · VCV1183958

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9906 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

White-Kernohan syndrome

Computational evidence

Protein change
AlphaMissense	0.9906	likely pathogenic ✓ concordant with ClinVar
REVEL	0.743	pathogenic-leaning
SaProt	LLR -13.71	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.4, phastCons 1
Regional constraint	o/e 0.71	unconstrained · MANE · 7,478 bp · p 1.9e-11 · regional, not allelic
Overall
CADD	27.1	PHRED · no single calibrated threshold — expert panels disagree

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: DDB1
Protein: p.Phe429Val
Coding: c.1285T>G
MANE Select: NM_001923
dbSNP: rs2134916397
Type: single nucleotide variant
Location: chr11:61316508 (GRCh38)
Gene constraint: LOEUF 0.195 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 92.14 · 219 PDB
Residue 429: a UniProt-annotated variant site (in whikers); the 'interaction with cdt1' region; the 'wd repeat beta-propeller b; interaction with cul4a' region; a β-strand

Full DDB1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

White-Kernohan syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DDB1 p.Arg188Trp Pathogenic/Likely pathogenic ★★ same condition
DDB1 p.Ile558Phe Uncertain significance ★★ ⚠ same condition
DDB1 p.Ile793Thr Uncertain significance ★★ ⚠ same condition
DDB1 p.Arg188Gln Pathogenic ★ same condition
DDB1 p.Glu213Lys Likely pathogenic ★ same condition
DDB1 p.Glu785Lys Likely pathogenic ★ same condition
DDB1 p.Ala968Ser Uncertain significance ★ ⚠ same condition
DDB1 p.Arg158Cys 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/ddb1-p-phe429val (accessed [today's date]).

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