Is DBF4 p.Asp384His (c.1150G>C) pathogenic?

DBF4 p.Asp384His (c.1150G>C) is classified Uncertain significance in DBF4 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-11). AlphaMissense: likely benign (0.1027); Ultra-rare (popmax 0.01%, amr).

How common is DBF4 p.Asp384His (c.1150G>C) in the general population?

DBF4 p.Asp384His (c.1150G>C) is ultra-rare (popmax 0.01%, amr) (gnomAD).

What do computational predictors say about DBF4 p.Asp384His (c.1150G>C)?

AlphaMissense predicts likely benign (score 0.1027) — an in-silico prediction, not a clinical call.

DBF4 p.Asp384His

c.1150G>C · VCV4237666

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1027 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.01%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1027	likely benign
REVEL	0.131	moderately benign-leaning
SaProt	LLR -6.31	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 2.4	GERP 1.8, phastCons 0.084
Regional constraint	o/e 0.84	unconstrained · MANE · 31 kb · p 8.6e-06 · regional, not allelic
Overall
CADD	8.13	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 0.01% Admixed American · 6/59,998 alleles

Filtering AF 0.00428% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00295%

Overall 0.00124% 20/1,613,820 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.01%	10,000
Remaining individualsnot grpmax-eligible	0.008%	12,496
African / African-American	0.00133%	74,908
European (non-Finnish)	0.000678%	147,491

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: DBF4
Protein: p.Asp384His
Coding: c.1150G>C
MANE Select: NM_006716
Type: single nucleotide variant
Location: chr7:87907288 (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-asp384his (accessed [today's date]).

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