Is DBN1 p.Pro665Leu (c.1994C>T) pathogenic?

DBN1 p.Pro665Leu (c.1994C>T) is classified Uncertain significance in DBN1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-07). AlphaMissense: likely benign (0.1758); Absent from gnomAD v4.1.

How common is DBN1 p.Pro665Leu (c.1994C>T) in the general population?

DBN1 p.Pro665Leu (c.1994C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DBN1 p.Pro665Leu (c.1994C>T)?

AlphaMissense predicts likely benign (score 0.1758) — an in-silico prediction, not a clinical call.

DBN1 p.Pro665Leu

c.1994C>T · VCV4009497

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1758 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1758	likely benign
REVEL	0.657	pathogenic-leaning
SaProt	LLR -7.79	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.6	GERP 0.98, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 10 kb · p 0.84 · regional, not allelic
Overall
CADD	26.1	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM P619L vs ClinVar P665L) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: DBN1
Protein: p.Pro665Leu
Coding: c.1994C>T
MANE Select: NM_001363541
Type: single nucleotide variant
Location: chr5:177457678 (GRCh38)
Gene constraint: LOEUF 0.347 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 62.93 · 5 PDB

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-pro665leu (accessed [today's date]).

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