Is DBF4 p.Val375Met (c.1123G>A) pathogenic?

DBF4 p.Val375Met (c.1123G>A) is classified Uncertain significance in DBF4 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-04). AlphaMissense: likely benign (0.0804); Very rare (popmax 0.00627%, nfe).

How common is DBF4 p.Val375Met (c.1123G>A) in the general population?

DBF4 p.Val375Met (c.1123G>A) is very rare (popmax 0.00627%, nfe) (gnomAD).

What do computational predictors say about DBF4 p.Val375Met (c.1123G>A)?

AlphaMissense predicts likely benign (score 0.0804) — an in-silico prediction, not a clinical call.

DBF4 p.Val375Met

c.1123G>A · VCV3838309

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0804 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00627%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0804	likely benign
REVEL	0.006	strongly benign-leaning
SaProt	LLR -7.07	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 0.2	GERP 2.1, phastCons 0.001
Regional constraint	o/e 0.84	unconstrained · MANE · 31 kb · p 8.6e-06 · regional, not allelic
Overall
CADD	14.95	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 0.00627% European (non-Finnish) · 74/1,179,886 alleles

Filtering AF 0.00511% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00468%

Overall 0.00471% 76/1,613,610 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00627%	15,944
Remaining individualsnot grpmax-eligible	0.0032%	31,234

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.Val375Met
Coding: c.1123G>A
MANE Select: NM_006716
Type: single nucleotide variant
Location: chr7:87907261 (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-val375met (accessed [today's date]).

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