Is DDB1 p.Ser345Phe (c.1034C>T) pathogenic?

DDB1 p.Ser345Phe (c.1034C>T) is classified Uncertain significance in DDB1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-25). AlphaMissense: ambiguous (0.4159); Absent from gnomAD v4.1; Associated with DDB1-related disorder.

What condition is associated with DDB1 p.Ser345Phe (c.1034C>T)?

DDB1 p.Ser345Phe (c.1034C>T) is associated with DDB1-related disorder (ClinVar).

How common is DDB1 p.Ser345Phe (c.1034C>T) in the general population?

DDB1 p.Ser345Phe (c.1034C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DDB1 p.Ser345Phe (c.1034C>T)?

AlphaMissense predicts ambiguous (score 0.4159) — an in-silico prediction, not a clinical call.

DDB1 p.Ser345Phe

c.1034C>T · rs1358257831 · VCV2631278

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4159 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

DDB1-related disorder

Computational evidence

Protein change
AlphaMissense	0.4159	ambiguous
REVEL	0.614	indeterminate
SaProt	LLR -11.25	damaging
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 12	GERP 2.1, phastCons 1
Regional constraint	o/e 0.28	constrained · MANE · 6,504 bp · p 1.8e-15 · regional, not allelic
Overall
CADD	29.5	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.Ser345Phe
Coding: c.1034C>T
MANE Select: NM_001923
dbSNP: rs1358257831
Type: single nucleotide variant
Location: chr11:61322384 (GRCh38)
Gene constraint: LOEUF 0.195 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 92.14 · 219 PDB
Residue 345: the 'interaction with cdt1' region; the 'wd repeat beta-propeller a' region

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

Disease context

DDB1-related disorder

Similar variants

DDB1 p.Cys732Phe Uncertain significance ★ same condition
DDB1 p.Gln1025Arg Uncertain significance ★ ⚠ same condition
DDB1 p.Met581Thr Uncertain significance same condition
DDB1 p.Thr20Ile Uncertain significance ⚠ same condition
DDB1 c.2069+5G>A Likely benign same condition
DDB1 c.2662-3C>A Likely benign same condition
DDB1 p.Ser25Leu Likely benign same condition
DDB1 p.Arg188Trp Pathogenic/Likely pathogenic ★★ 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/ddb1-p-ser345phe (accessed [today's date]).

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