Is DBF4 p.Asp254Glu (c.762T>G) pathogenic?

DBF4 p.Asp254Glu (c.762T>G) is classified Uncertain significance in DBF4 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-11-12). AlphaMissense: ambiguous (0.3589); Absent from gnomAD v4.1.

How common is DBF4 p.Asp254Glu (c.762T>G) in the general population?

DBF4 p.Asp254Glu (c.762T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DBF4 p.Asp254Glu (c.762T>G)?

AlphaMissense predicts ambiguous (score 0.3589) — an in-silico prediction, not a clinical call.

DBF4 p.Asp254Glu

c.762T>G · rs2535379037 · VCV2260942

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3589 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3589	ambiguous
REVEL	0.05	moderately benign-leaning
SaProt	LLR -8.06	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	Δ0.27	donor loss · deltas
Constraint at this position
Conservation	phyloP 1.5	GERP 3, phastCons 1
Regional constraint	o/e 0.84	unconstrained · MANE · 31 kb · p 8.6e-06 · regional, not allelic
Overall
CADD	15.05	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: DBF4
Protein: p.Asp254Glu
Coding: c.762T>G
MANE Select: NM_006716
dbSNP: rs2535379037
Type: single nucleotide variant
Location: chr7:87900302 (GRCh38)
Gene constraint: LOEUF 0.475 · pLI 0.99 (gnomAD)
Structure: AlphaFold pLDDT 55.17 · 7 PDB

Full DBF4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DBF4 p.Ile18= Benign ★★ same type
DBF4 p.Lys579Glu Benign ★★ same type
DBF4 p.Ala661Val Uncertain significance ★ ⚠ same type
DBF4 p.Arg101Gln Uncertain significance ★ ⚠ same type
DBF4 p.Arg214Lys Uncertain significance ★ ⚠ same type
DBF4 p.Arg26Gly Uncertain significance ★ ⚠ same type
DBF4 p.Arg576Gln Uncertain significance ★ ⚠ same type
DBF4 p.Arg599Gly 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/dbf4-p-asp254glu (accessed [today's date]).

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