Is DBF4 p.Lys190Glu (c.568A>G) pathogenic?

DBF4 p.Lys190Glu (c.568A>G) is classified Uncertain significance in DBF4 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-16). AlphaMissense: ambiguous (0.3753); Ultra-rare (popmax 0.0452%, amr).

How common is DBF4 p.Lys190Glu (c.568A>G) in the general population?

DBF4 p.Lys190Glu (c.568A>G) is ultra-rare (popmax 0.0452%, amr) (gnomAD).

What do computational predictors say about DBF4 p.Lys190Glu (c.568A>G)?

AlphaMissense predicts ambiguous (score 0.3753) — an in-silico prediction, not a clinical call.

DBF4 p.Lys190Glu

c.568A>G · VCV4237664

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3753 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0452%, amr)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3753	ambiguous
REVEL	0.193	benign-leaning
SaProt	LLR -7.12	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · A>T here scores Δ0.61 · evaluated, not missing
Constraint at this position
Conservation	phyloP 9.3	GERP 3.8, phastCons 1
Regional constraint	o/e 0.84	unconstrained · MANE · 31 kb · p 8.6e-06 · regional, not allelic
Overall
CADD	25.2	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

Grpmax group 0.0452% Admixed American · 22/48,676 alleles

Filtering AF 0.0306% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0258%

Overall 0.00179% 28/1,561,782 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0452%	2,213
Remaining individualsnot grpmax-eligible	0.00333%	30,032
European (non-Finnish)	0.000346%	289,199

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.Lys190Glu
Coding: c.568A>G
MANE Select: NM_006716
Type: single nucleotide variant
Location: chr7:87888030 (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-lys190glu (accessed [today's date]).

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