Is DMBT1 p.Pro596Ser (c.1786C>T) pathogenic?

DMBT1 p.Pro596Ser (c.1786C>T) is classified Uncertain significance in DMBT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-04). AlphaMissense: likely benign (0.0891); Very rare (popmax 0.00755%, nfe).

How common is DMBT1 p.Pro596Ser (c.1786C>T) in the general population?

DMBT1 p.Pro596Ser (c.1786C>T) is very rare (popmax 0.00755%, nfe) (gnomAD).

What do computational predictors say about DMBT1 p.Pro596Ser (c.1786C>T)?

AlphaMissense predicts likely benign (score 0.0891) — an in-silico prediction, not a clinical call.

DMBT1 p.Pro596Ser

c.1786C>T · rs372308924 · VCV2593867

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0891 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00755%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0891	likely benign
REVEL	0.016	strongly benign-leaning
SaProt	LLR -4.65	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -13	GERP -3.1
Regional constraint	o/e 1.17	unconstrained · MANE · 40 kb · p 3.3e-08 · regional, not allelic
Overall
CADD	0.047	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00755% European (non-Finnish) · 88/1,165,660 alleles

Filtering AF 0.00622% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0058%

Overall 0.00561% 89/1,587,668 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00755%	13,246
African / African-American	0.00134%	74,496

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: DMBT1
Protein: p.Pro596Ser
Coding: c.1786C>T
MANE Select: NM_001377530
dbSNP: rs372308924
Type: single nucleotide variant
Location: chr10:122588946 (GRCh38)
Gene constraint: LOEUF 0.904 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.29 · 6 PDB

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-pro596ser (accessed [today's date]).

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