Is DMBT1 p.Ser1789Pro (c.5365T>C) pathogenic?

DMBT1 p.Ser1789Pro (c.5365T>C) is classified Uncertain significance in DMBT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-11). AlphaMissense: likely pathogenic (0.7511); Absent from gnomAD v4.1.

How common is DMBT1 p.Ser1789Pro (c.5365T>C) in the general population?

DMBT1 p.Ser1789Pro (c.5365T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DMBT1 p.Ser1789Pro (c.5365T>C)?

AlphaMissense predicts likely pathogenic (score 0.7511) — an in-silico prediction, not a clinical call.

DMBT1 p.Ser1789Pro

c.5365T>C · VCV4012219

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7511 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.7511	likely pathogenic
REVEL	0.174	moderately benign-leaning
SaProt	LLR -12.56	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -20	GERP -1.9
Regional constraint	o/e 0.99	unconstrained · MANE · 40 kb · p 0.84 · regional, not allelic
Overall
CADD	20.5	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 S1660P vs ClinVar S1789P) — 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: DMBT1
Protein: p.Ser1789Pro
Coding: c.5365T>C
MANE Select: NM_001377530
Type: single nucleotide variant
Location: chr10:122621137 (GRCh38)
Gene constraint: LOEUF 0.904 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.29 · 6 PDB
Residue 1789: the cub 1 domain; a disulfide bond

Full DMBT1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DMBT1 p.Asp696Val Uncertain significance ★★ ⚠ same type
DMBT1 p.His805Asn Uncertain significance ★★ ⚠ same type
DMBT1 p.Arg670Cys Benign ★★ ⚠ same type
DMBT1 p.Asp1796Glu Benign ★★ ⚠ same type
DMBT1 p.Asp635Asn Benign ★★ ⚠ same type
DMBT1 p.Asp668Asn Benign ★★ ⚠ same type
DMBT1 p.Asp696= Likely benign ★★ same type
DMBT1 p.Gln1656Arg Benign ★★ 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/dmbt1-p-ser1789pro (accessed [today's date]).

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