Is DBNDD1 p.Val25Ile (c.73G>A) pathogenic?

DBNDD1 p.Val25Ile (c.73G>A) is classified Uncertain significance in DBNDD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-14). AlphaMissense: likely benign (0.0711); Ultra-rare (popmax 0.0493%, mid).

How common is DBNDD1 p.Val25Ile (c.73G>A) in the general population?

DBNDD1 p.Val25Ile (c.73G>A) is ultra-rare (popmax 0.0493%, mid) (gnomAD).

What do computational predictors say about DBNDD1 p.Val25Ile (c.73G>A)?

AlphaMissense predicts likely benign (score 0.0711) — an in-silico prediction, not a clinical call.

DBNDD1 p.Val25Ile

c.73G>A · VCV4237730

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0711 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0493%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0711	likely benign
REVEL	0.08	moderately benign-leaning
SaProt	LLR -7.30	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 0.49	GERP -2.2, phastCons 0.089
Regional constraint	o/e 1.02	unconstrained · MANE · 13 kb · p 0.74 · regional, not allelic
Overall
CADD	16.83	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 0.0493% Middle Eastern · 3/6,082 alleles

Filtering AF 0.0134% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00716%

Overall 0.00434% 70/1,612,948 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0493%	2,027
African / African-American	0.00534%	18,736
European (non-Finnish)	0.00525%	19,032
Admixed American	0.00167%	60,002

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: DBNDD1
Protein: p.Val25Ile
Coding: c.73G>A
MANE Select: NM_001042610
Type: single nucleotide variant
Location: chr16:90009389 (GRCh38)
Gene constraint: LOEUF 1.46 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 61.46
Residue 25: the 'disordered' region

Full DBNDD1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DBNDD1 c.32-545G>A Uncertain significance ★ same type
DBNDD1 c.32-547C>T Uncertain significance ★ same type
DBNDD1 c.32-548G>A Uncertain significance ★ same type
DBNDD1 p.Ala143Thr Uncertain significance ★ ⚠ same type
DBNDD1 p.Ala27Thr Uncertain significance ★ ⚠ same type
DBNDD1 p.Arg113Gln Uncertain significance ★ ⚠ same type
DBNDD1 p.Arg118His Uncertain significance ★ ⚠ same type
DBNDD1 p.Arg141Gln 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/dbndd1-p-val25ile (accessed [today's date]).

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