Is DBF4B p.Leu372Val (c.1114C>G) pathogenic?

DBF4B p.Leu372Val (c.1114C>G) is classified Uncertain significance in DBF4B (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-07). AlphaMissense: likely benign (0.0887); Ultra-rare (popmax 0.024%, afr).

How common is DBF4B p.Leu372Val (c.1114C>G) in the general population?

DBF4B p.Leu372Val (c.1114C>G) is ultra-rare (popmax 0.024%, afr) (gnomAD).

What do computational predictors say about DBF4B p.Leu372Val (c.1114C>G)?

AlphaMissense predicts likely benign (score 0.0887) — an in-silico prediction, not a clinical call.

DBF4B p.Leu372Val

c.1114C>G · VCV4009470

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0887 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.024%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0887	likely benign
REVEL	0.079	moderately benign-leaning
SaProt	LLR -7.10	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 -0.21	GERP -4.4
Regional constraint	o/e 0.90	unconstrained · MANE · 21 kb · p 0.0076 · regional, not allelic
Overall
CADD	1.848	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 0.024% African / African-American · 18/75,032 alleles

Filtering AF 0.0154% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0128%

Overall 0.00205% 33/1,613,278 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.024%	4,168
Remaining individualsnot grpmax-eligible	0.0192%	5,206
European (non-Finnish)	0.000254%	393,173

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: DBF4B
Protein: p.Leu372Val
Coding: c.1114C>G
MANE Select: NM_145663
Type: single nucleotide variant
Location: chr17:44748390 (GRCh38)
Gene constraint: LOEUF 1.003 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 55.60
Residue 372: the 'disordered' region

Full DBF4B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

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DBF4B p.Ala331Val Uncertain significance ★ ⚠ same type
DBF4B p.Ala361Thr Uncertain significance ★ ⚠ same type
DBF4B p.Ala383Thr Uncertain significance ★ ⚠ same type
DBF4B p.Ala499Ser Uncertain significance ★ ⚠ same type
DBF4B p.Ala69Thr Uncertain significance ★ ⚠ same type
DBF4B p.Arg131Ser 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/dbf4b-p-leu372val (accessed [today's date]).

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