Is DBF4B p.Arg92Cys (c.274C>T) pathogenic?

DBF4B p.Arg92Cys (c.274C>T) is classified Uncertain significance in DBF4B (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-31). AlphaMissense: likely benign (0.2368); Ultra-rare (popmax 0.0165%, mid).

How common is DBF4B p.Arg92Cys (c.274C>T) in the general population?

DBF4B p.Arg92Cys (c.274C>T) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

What do computational predictors say about DBF4B p.Arg92Cys (c.274C>T)?

AlphaMissense predicts likely benign (score 0.2368) — an in-silico prediction, not a clinical call.

DBF4B p.Arg92Cys

c.274C>T · VCV4009465

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2368 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2368	likely benign
REVEL	0.264	benign-leaning
SaProt	LLR -12.53	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 2.5	GERP 0.62, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 21 kb · p 0.0076 · regional, not allelic
Overall
CADD	25.3	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 0.0165% Middle Eastern · 1/6,044 alleles

Filtering AF 0.00816% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00634%

Overall 0.00149% 24/1,613,894 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,044
African / African-American	0.0147%	6,807
Remaining individualsnot grpmax-eligible	0.0048%	20,823
East Asian	0.00446%	22,445
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,606
Admixed American	0.00167%	59,982
European (non-Finnish)	0.000424%	236,005

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.Arg92Cys
Coding: c.274C>T
MANE Select: NM_145663
Type: single nucleotide variant
Location: chr17:44729953 (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.Arg92His 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-arg92cys (accessed [today's date]).

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