Is DBNL p.Arg191Trp (c.571C>T) pathogenic?

DBNL p.Arg191Trp (c.571C>T) is classified Uncertain significance in DBNL (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-10). AlphaMissense: likely benign (0.1393); Very rare (popmax 0.00584%, amr).

How common is DBNL p.Arg191Trp (c.571C>T) in the general population?

DBNL p.Arg191Trp (c.571C>T) is very rare (popmax 0.00584%, amr) (gnomAD).

What do computational predictors say about DBNL p.Arg191Trp (c.571C>T)?

AlphaMissense predicts likely benign (score 0.1393) — an in-silico prediction, not a clinical call.

DBNL p.Arg191Trp

c.571C>T · VCV4237739

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1393 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00584%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1393	likely benign
REVEL	0.081	moderately benign-leaning
SaProt	LLR -13.41	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.4	GERP -2.4, phastCons 0.46
Regional constraint	o/e 0.86	unconstrained · MANE · 16 kb · p 0.00052 · regional, not allelic
Overall
CADD	22.8	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 0.00584% Admixed American · 3/51,346 alleles

Filtering AF 0.00155% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00083%

Overall 0.00116% 18/1,557,168 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00584%	17,115
Ashkenazi Jewishnot grpmax-eligible	0.00349%	28,678
Remaining individualsnot grpmax-eligible	0.00166%	60,342
African / African-American	0.00136%	73,544
South Asian	0.00118%	84,528
European (non-Finnish)	0.000956%	104,626

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.Arg191Trp
Coding: c.571C>T
MANE Select: NM_001014436
Type: single nucleotide variant
Location: chr7:44058147 (GRCh38)
Gene constraint: LOEUF 0.782 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.60 · 1 PDB

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

Similar variants

PGAM2 p.Arg191Gln Uncertain significance ★ ⚠ same residue
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

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-arg191trp (accessed [today's date]).

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