Is DMBT1 p.Ser1095Pro (c.3283T>C) pathogenic?

DMBT1 p.Ser1095Pro (c.3283T>C) is classified Uncertain significance in DMBT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-11). AlphaMissense: likely benign (0.0998); Rare (popmax 0.166%, afr).

How common is DMBT1 p.Ser1095Pro (c.3283T>C) in the general population?

DMBT1 p.Ser1095Pro (c.3283T>C) is rare (popmax 0.166%, afr) (gnomAD).

What do computational predictors say about DMBT1 p.Ser1095Pro (c.3283T>C)?

AlphaMissense predicts likely benign (score 0.0998) — an in-silico prediction, not a clinical call.

DMBT1 p.Ser1095Pro

c.3283T>C · VCV4241301

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0998 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.166%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0998	likely benign
REVEL	0.032	moderately benign-leaning
SaProt	LLR -9.00	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 -9.8	GERP -2.2
Regional constraint	o/e 1.17	unconstrained · MANE · 40 kb · p 3.3e-08 · regional, not allelic
Overall
CADD	0.124	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 0.166% African / African-American · 115/69,466 alleles

Filtering AF 0.141% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.132%

Overall 0.0191% 304/1,592,894 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.166%	604
Amishnot grpmax-eligible	0.112%	890
Admixed American	0.0637%	1,570
South Asian	0.0398%	2,513
East Asian	0.0344%	2,903
Middle Eastern	0.0334%	2,996
Remaining individualsnot grpmax-eligible	0.0146%	6,871
Finnishnot grpmax-eligible	0.011%	9,054
European (non-Finnish)	0.00699%	14,316
Ashkenazi Jewishnot grpmax-eligible	0.0068%	14,713

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.Ser1095Pro
Coding: c.3283T>C
MANE Select: NM_001377530
Type: single nucleotide variant
Location: chr10:122600066 (GRCh38)
Gene constraint: LOEUF 0.904 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.29 · 6 PDB
Residue 1095: a UniProt-annotated variant site (in); the 'disordered' region

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-ser1095pro (accessed [today's date]).

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