Is DBF4B p.Arg92His (c.275G>A) pathogenic?

DBF4B p.Arg92His (c.275G>A) is classified Uncertain significance in DBF4B (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-25). AlphaMissense: likely benign (0.1835); Ultra-rare (popmax 0.029%, eas).

How common is DBF4B p.Arg92His (c.275G>A) in the general population?

DBF4B p.Arg92His (c.275G>A) is ultra-rare (popmax 0.029%, eas) (gnomAD).

What do computational predictors say about DBF4B p.Arg92His (c.275G>A)?

AlphaMissense predicts likely benign (score 0.1835) — an in-silico prediction, not a clinical call.

DBF4B p.Arg92His

c.275G>A · VCV4009468

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1835 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.029%, eas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1835	likely benign
REVEL	0.123	moderately benign-leaning
SaProt	LLR -11.49	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
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	23.9	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 0.029% East Asian · 13/44,882 alleles

Filtering AF 0.0171% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0136%

Overall 0.00328% 53/1,613,990 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.029%	3,452
Middle Eastern	0.0166%	6,012
South Asian	0.00769%	13,009
Finnishnot grpmax-eligible	0.00469%	21,333
African / African-American	0.004%	25,003
Remaining individualsnot grpmax-eligible	0.0032%	31,250
European (non-Finnish)	0.00195%	51,305
Admixed American	0.00167%	59,998

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.Arg92His
Coding: c.275G>A
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.Arg92Leu 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-arg92his (accessed [today's date]).

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