Is DBF4B p.Arg92Leu (c.275G>T) pathogenic?

DBF4B p.Arg92Leu (c.275G>T) is classified Uncertain significance in DBF4B (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-29). AlphaMissense: ambiguous (0.4596); Rare (popmax 0.92%, afr).

How common is DBF4B p.Arg92Leu (c.275G>T) in the general population?

DBF4B p.Arg92Leu (c.275G>T) is rare (popmax 0.92%, afr) (gnomAD).

What do computational predictors say about DBF4B p.Arg92Leu (c.275G>T)?

AlphaMissense predicts ambiguous (score 0.4596) — an in-silico prediction, not a clinical call.

DBF4B p.Arg92Leu

c.275G>T · VCV4237692

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4596 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.92%, afr)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4596	ambiguous
REVEL	0.154	moderately benign-leaning
SaProt	LLR -11.88	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.3	GERP -0.68, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 21 kb · p 0.0076 · regional, not allelic
Overall
CADD	21.7	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 0.92% African / African-American · 690/75,008 alleles

Filtering AF 0.863% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.84%

Overall 0.047% 758/1,613,988 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.92%	109
Remaining individualsnot grpmax-eligible	0.0576%	1,736
Middle Eastern	0.0333%	3,006
Admixed American	0.0267%	3,750
European (non-Finnish)	0.0011%	90,770
South Asian	0.0011%	91,060

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.Arg92Leu
Coding: c.275G>T
MANE Select: NM_145663
Type: single nucleotide variant
Location: chr17:44729954 (GRCh38)
Gene constraint: LOEUF 1.003 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 55.60
Residue 92: the brct domain

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

Similar variants

DBF4B p.Arg92Cys Uncertain significance ★ ⚠ same residue
DBF4B p.Arg92His Uncertain significance ★ ⚠ same residue
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

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-arg92leu (accessed [today's date]).

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