Is DBNL p.Val243Ala (c.728T>C) pathogenic?

DBNL p.Val243Ala (c.728T>C) is classified Uncertain significance in DBNL (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-17). AlphaMissense: likely benign (0.067); Very rare (popmax 8.47e-05%, nfe).

How common is DBNL p.Val243Ala (c.728T>C) in the general population?

DBNL p.Val243Ala (c.728T>C) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about DBNL p.Val243Ala (c.728T>C)?

AlphaMissense predicts likely benign (score 0.067) — an in-silico prediction, not a clinical call.

DBNL p.Val243Ala

c.728T>C · VCV4658543

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.067 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.067	likely benign
REVEL	0.079	moderately benign-leaning
SaProt	LLR -4.94	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 -0.41	GERP -1.1
Regional constraint	o/e 0.86	unconstrained · MANE · 16 kb · p 0.00052 · regional, not allelic
Overall
CADD	7.503	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 8.47e-05% European (non-Finnish) · 1/1,180,038 alleles

Overall 6.84e-05% 1/1,461,876 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: DBNL
Protein: p.Val243Ala
Coding: c.728T>C
MANE Select: NM_001014436
Type: single nucleotide variant
Location: chr7:44058455 (GRCh38)
Gene constraint: LOEUF 0.782 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.60 · 1 PDB
Residue 243: the 'disordered' region

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

Similar variants

PGAM2 p.Trp78Ter Pathogenic/Likely pathogenic ★★ same type
PGAM2 p.Ala143Thr Uncertain significance ★★ ⚠ same type
PGAM2 p.Ala252Asp Uncertain significance ★★ ⚠ same type
PGAM2 p.Arg10Trp Uncertain significance ★★ ⚠ same type
PGAM2 p.Arg162Gln Uncertain significance ★★ ⚠ same type
PGAM2 p.Arg162Pro Uncertain significance ★★ ⚠ same type
PGAM2 p.Arg240Gln Uncertain significance ★★ ⚠ same type
PGAM2 p.Arg5His 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/dbnl-p-val243ala (accessed [today's date]).

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