Is DBF4B p.Lys38Gln (c.112A>C) pathogenic?

DBF4B p.Lys38Gln (c.112A>C) is classified Uncertain significance in DBF4B (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-26). AlphaMissense: likely benign (0.1237); Very rare (popmax 0.00133%, afr).

How common is DBF4B p.Lys38Gln (c.112A>C) in the general population?

DBF4B p.Lys38Gln (c.112A>C) is very rare (popmax 0.00133%, afr) (gnomAD).

What do computational predictors say about DBF4B p.Lys38Gln (c.112A>C)?

AlphaMissense predicts likely benign (score 0.1237) — an in-silico prediction, not a clinical call.

DBF4B p.Lys38Gln

c.112A>C · VCV4658516

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1237 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1237	likely benign
REVEL	0.08	moderately benign-leaning
SaProt	LLR -6.04	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 3.4	GERP 1, phastCons 0.98
Regional constraint	o/e 1.29	unconstrained · MANE · 14 kb · p 0.04 · regional, not allelic
Overall
CADD	20.6	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 0.00133% African / African-American · 1/74,940 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.00031% 5/1,614,070 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00133%	74,940
European (non-Finnish)	0.000339%	295,009

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.Lys38Gln
Coding: c.112A>C
MANE Select: NM_145663
Type: single nucleotide variant
Location: chr17:44722909 (GRCh38)
Gene constraint: LOEUF 1.003 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 55.60

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

Similar variants

DBF4B p.Val89Met Uncertain significance ★★ ⚠ same type
DBF4B p.Ala197Val Uncertain significance ★ ⚠ same type
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-lys38gln (accessed [today's date]).

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