Is DBNL p.Pro337Thr (c.1009C>A) pathogenic?

DBNL p.Pro337Thr (c.1009C>A) is classified Uncertain significance in DBNL (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-02). AlphaMissense: likely benign (0.0709); Very rare (popmax 0.00334%, amr).

How common is DBNL p.Pro337Thr (c.1009C>A) in the general population?

DBNL p.Pro337Thr (c.1009C>A) is very rare (popmax 0.00334%, amr) (gnomAD).

What do computational predictors say about DBNL p.Pro337Thr (c.1009C>A)?

AlphaMissense predicts likely benign (score 0.0709) — an in-silico prediction, not a clinical call.

DBNL p.Pro337Thr

c.1009C>A · VCV4658552

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0709 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00334%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0709	likely benign
REVEL	0.084	moderately benign-leaning
SaProt	LLR -10.44	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 2.2	GERP 0.46, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 16 kb · p 0.00052 · regional, not allelic
Overall
CADD	16.17	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 0.00334% Admixed American · 2/59,960 alleles

Filtering AF 0.000553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000207%

Overall 0.000497% 8/1,609,782 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00334%	29,980
European (non-Finnish)	0.000509%	196,647

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.Pro337Thr
Coding: c.1009C>A
MANE Select: NM_001014436
Type: single nucleotide variant
Location: chr7:44059620 (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.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-pro337thr (accessed [today's date]).

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