Is DBN1 p.Pro378= (c.1134C>T) pathogenic?

DBN1 p.Pro378= (c.1134C>T) is classified Benign in DBN1 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-07-23). Low-frequency (popmax 2.43%, afr).

How common is DBN1 p.Pro378= (c.1134C>T) in the general population?

DBN1 p.Pro378= (c.1134C>T) is low-frequency (popmax 2.43%, afr) (gnomAD).

DBN1 p.Pro378=

c.1134C>T · rs116548591 · VCV768052

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

low-frequency (popmax 2.43%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.27	GERP -2.3, phastCons 0.9
Overall
CADD	4.49	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 2.43% African / African-American · 1,819/74,894 alleles

Filtering AF 2.34% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.3%

Overall 0.126% 2,034/1,610,820 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	2.43%	41
Middle Eastern	0.332%	301
Remaining individualsnot grpmax-eligible	0.136%	734
Admixed American	0.0972%	1,029
European (non-Finnish)	0.00416%	24,065
South Asian	0.0033%	30,336

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.Pro378=
Coding: c.1134C>T
MANE Select: NM_001363541
dbSNP: rs116548591
Type: single nucleotide variant
Location: chr5:177459228 (GRCh38)
Gene constraint: LOEUF 0.347 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 62.93 · 5 PDB
Residue 378: the 'disordered' region

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-pro378 (accessed [today's date]).

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