Is DBF4B p.Val85Ile (c.253G>A) pathogenic?

DBF4B p.Val85Ile (c.253G>A) is classified Uncertain significance in DBF4B (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-02). AlphaMissense: likely benign (0.1316); Very rare (popmax 0.00356%, nfe).

How common is DBF4B p.Val85Ile (c.253G>A) in the general population?

DBF4B p.Val85Ile (c.253G>A) is very rare (popmax 0.00356%, nfe) (gnomAD).

What do computational predictors say about DBF4B p.Val85Ile (c.253G>A)?

AlphaMissense predicts likely benign (score 0.1316) — an in-silico prediction, not a clinical call.

DBF4B p.Val85Ile

c.253G>A · rs750811439 · VCV2592905

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1316 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00356%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1316	likely benign
REVEL	0.055	moderately benign-leaning
SaProt	LLR -6.93	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 4.9	GERP 0.15, phastCons 1
Regional constraint	o/e 0.50	unconstrained · MANE · 7,026 bp · p 0.00015 · regional, not allelic
Overall
CADD	19.85	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 0.00356% European (non-Finnish) · 42/1,180,024 alleles

Filtering AF 0.00267% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00236%

Overall 0.0026% 42/1,613,970 alleles · very rare

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.Val85Ile
Coding: c.253G>A
MANE Select: NM_145663
dbSNP: rs750811439
Type: single nucleotide variant
Location: chr17:44729932 (GRCh38)
Gene constraint: LOEUF 1.003 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 55.60
Residue 85: the brct domain

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-val85ile (accessed [today's date]).

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