Is DBF4B p.Val89Met (c.265G>A) pathogenic?

DBF4B p.Val89Met (c.265G>A) is classified Uncertain significance in DBF4B (ClinVar, Multiple submitters, 2 submitters; last evaluated 2021-12-14). AlphaMissense: likely pathogenic (0.8858); Ultra-rare (popmax 0.0331%, mid).

How common is DBF4B p.Val89Met (c.265G>A) in the general population?

DBF4B p.Val89Met (c.265G>A) is ultra-rare (popmax 0.0331%, mid) (gnomAD).

What do computational predictors say about DBF4B p.Val89Met (c.265G>A)?

AlphaMissense predicts likely pathogenic (score 0.8858) — an in-silico prediction, not a clinical call.

DBF4B p.Val89Met

c.265G>A · rs369201138 · VCV2267380

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.8858 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0331%, mid)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8858	likely pathogenic · top 7% in DBF4B
REVEL	0.2	benign-leaning
SaProt	LLR -14.42	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.9	GERP 2.5, phastCons 1
Regional constraint	o/e 0.50	unconstrained · MANE · 7,026 bp · p 0.00015 · regional, not allelic
Overall
CADD	25.5	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 0.0331% Middle Eastern · 2/6,046 alleles

Filtering AF 0.00583% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00242%

Overall 0.000496% 8/1,613,930 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0331%	3,023
East Asian	0.00223%	44,894
Admixed American	0.00167%	59,974
South Asian	0.0011%	91,082
European (non-Finnish)	0.000254%	393,340

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.Val89Met
Coding: c.265G>A
MANE Select: NM_145663
dbSNP: rs369201138
Type: single nucleotide variant
Location: chr17:44729944 (GRCh38)
Gene constraint: LOEUF 1.003 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 55.60
Residue 89: the brct domain

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

Similar variants

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
DBF4B p.Arg144Lys 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-val89met (accessed [today's date]).

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