Is DBF4 p.Pro417Arg (c.1250C>G) pathogenic?

DBF4 p.Pro417Arg (c.1250C>G) is classified Uncertain significance in DBF4 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-14). AlphaMissense: likely benign (0.0935); Ultra-rare (popmax 0.0274%, sas).

How common is DBF4 p.Pro417Arg (c.1250C>G) in the general population?

DBF4 p.Pro417Arg (c.1250C>G) is ultra-rare (popmax 0.0274%, sas) (gnomAD).

What do computational predictors say about DBF4 p.Pro417Arg (c.1250C>G)?

AlphaMissense predicts likely benign (score 0.0935) — an in-silico prediction, not a clinical call.

DBF4 p.Pro417Arg

c.1250C>G · rs775030398 · VCV2599444

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0935 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0274%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0935	likely benign
REVEL	0.027	moderately benign-leaning
SaProt	LLR -6.67	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 0.35	GERP 2.8
Regional constraint	o/e 0.84	unconstrained · MANE · 31 kb · p 8.6e-06 · regional, not allelic
Overall
CADD	13.6	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 0.0274% South Asian · 25/91,076 alleles

Filtering AF 0.019% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0163%

Overall 0.00167% 27/1,613,886 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0274%	3,643
Admixed American	0.00167%	59,992
Remaining individualsnot grpmax-eligible	0.0016%	62,482

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.Pro417Arg
Coding: c.1250C>G
MANE Select: NM_006716
dbSNP: rs775030398
Type: single nucleotide variant
Location: chr7:87907388 (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-pro417arg (accessed [today's date]).

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