Is DBN1 p.Val514Ile (c.1540G>A) pathogenic?

DBN1 p.Val514Ile (c.1540G>A) is classified Uncertain significance in DBN1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-22). AlphaMissense: likely benign (0.0683); Ultra-rare (popmax 0.0125%, nfe).

How common is DBN1 p.Val514Ile (c.1540G>A) in the general population?

DBN1 p.Val514Ile (c.1540G>A) is ultra-rare (popmax 0.0125%, nfe) (gnomAD).

What do computational predictors say about DBN1 p.Val514Ile (c.1540G>A)?

AlphaMissense predicts likely benign (score 0.0683) — an in-silico prediction, not a clinical call.

DBN1 p.Val514Ile

c.1540G>A · rs748935744 · VCV3080182

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0683 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0125%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0683	likely benign
REVEL	0.002	strongly benign-leaning
SaProt	LLR -7.32	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 -6.4	GERP -3.5
Regional constraint	o/e 1.01	unconstrained · MANE · 10 kb · p 0.84 · regional, not allelic
Overall
CADD	0.066	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.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM V468I vs ClinVar V514I) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0125% European (non-Finnish) · 147/1,180,020 alleles

Filtering AF 0.0108% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0102%

Overall 0.00997% 161/1,614,042 alleles · ultra-rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.016%	6,248
European (non-Finnish)grpmax	0.0125%	8,027
Admixed American	0.005%	20,001
South Asian	0.0011%	91,086

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: DBN1
Protein: p.Val514Ile
Coding: c.1540G>A
MANE Select: NM_001363541
dbSNP: rs748935744
Type: single nucleotide variant
Location: chr5:177458432 (GRCh38)
Gene constraint: LOEUF 0.347 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 62.93 · 5 PDB

Full DBN1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DBN1 c.86+1283G>A Uncertain significance ★ same type
DBN1 c.86+1286G>A Uncertain significance ★ same type
DBN1 c.86+1299A>T Uncertain significance ★ same type
DBN1 p.Ala126Val Uncertain significance ★ ⚠ same type
DBN1 p.Ala244Val Uncertain significance ★ ⚠ same type
DBN1 p.Ala27Thr Uncertain significance ★ ⚠ same type
DBN1 p.Ala455Val Uncertain significance ★ ⚠ same type
DBN1 p.Ala485Thr 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/dbn1-p-val514ile (accessed [today's date]).

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