Is DMBT1 p.Pro1699Ser (c.5095C>T) pathogenic?

DMBT1 p.Pro1699Ser (c.5095C>T) is classified Uncertain significance in DMBT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-03). AlphaMissense: likely benign (0.1693); Ultra-rare (popmax 0.0507%, afr).

How common is DMBT1 p.Pro1699Ser (c.5095C>T) in the general population?

DMBT1 p.Pro1699Ser (c.5095C>T) is ultra-rare (popmax 0.0507%, afr) (gnomAD).

What do computational predictors say about DMBT1 p.Pro1699Ser (c.5095C>T)?

AlphaMissense predicts likely benign (score 0.1693) — an in-silico prediction, not a clinical call.

DMBT1 p.Pro1699Ser

c.5095C>T · rs775173681 · VCV2519264

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1693 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0507%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1693	likely benign
REVEL	0.17	moderately benign-leaning
SaProt	LLR -10.48	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -20	GERP -1.6
Regional constraint	o/e 0.99	unconstrained · MANE · 40 kb · p 0.84 · regional, not allelic
Overall
CADD	12.88	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 P1570S vs ClinVar P1699S) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0507% African / African-American · 38/74,902 alleles

Filtering AF 0.038% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0335%

Overall 0.00248% 40/1,613,660 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0507%	1,971
Remaining individualsnot grpmax-eligible	0.0016%	62,450
South Asian	0.0011%	91,072

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.Pro1699Ser
Coding: c.5095C>T
MANE Select: NM_001377530
dbSNP: rs775173681
Type: single nucleotide variant
Location: chr10:122618220 (GRCh38)
Gene constraint: LOEUF 0.904 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.29 · 6 PDB
Residue 1699: the srcr 13 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-pro1699ser (accessed [today's date]).

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