Is DMBT1 p.Arg2201Cys (c.6601C>T) pathogenic?

DMBT1 p.Arg2201Cys (c.6601C>T) is classified Uncertain significance in DMBT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-23). AlphaMissense: likely benign (0.1904); Very rare (popmax 0.00398%, nfe).

How common is DMBT1 p.Arg2201Cys (c.6601C>T) in the general population?

DMBT1 p.Arg2201Cys (c.6601C>T) is very rare (popmax 0.00398%, nfe) (gnomAD).

What do computational predictors say about DMBT1 p.Arg2201Cys (c.6601C>T)?

AlphaMissense predicts likely benign (score 0.1904) — an in-silico prediction, not a clinical call.

DMBT1 p.Arg2201Cys

c.6601C>T · rs374738106 · VCV3083058

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1904 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00398%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1904	likely benign
REVEL	0.111	moderately benign-leaning
SaProt	LLR -8.59	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 0.8	GERP -0.5
Regional constraint	o/e 0.99	unconstrained · MANE · 40 kb · p 0.84 · regional, not allelic
Overall
CADD	18.47	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.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM R2072C vs ClinVar R2201C) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00398% European (non-Finnish) · 47/1,179,884 alleles

Filtering AF 0.00307% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00275%

Overall 0.00341% 55/1,613,870 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0064%	15,617
European (non-Finnish)grpmax	0.00398%	25,104
Admixed American	0.00333%	29,998
Finnishnot grpmax-eligible	0.00156%	64,028
South Asian	0.0011%	91,086

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Arg2201Cys
Coding: c.6601C>T
MANE Select: NM_001377530
dbSNP: rs374738106
Type: single nucleotide variant
Location: chr10:122636043 (GRCh38)
Gene constraint: LOEUF 0.904 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.29 · 6 PDB
Residue 2201: the zp domain

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

Similar variants

DMBT1 p.Arg2201Ser Uncertain significance ★ ⚠ same residue
DMBT1 p.Arg2201His Likely benign ★ same residue
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

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-arg2201cys (accessed [today's date]).

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