Is DMBT1 p.Arg562His (c.1685G>A) pathogenic?

DMBT1 p.Arg562His (c.1685G>A) is classified Uncertain significance in DMBT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-10). AlphaMissense: likely benign (0.1744); Rare (popmax 0.114%, sas).

How common is DMBT1 p.Arg562His (c.1685G>A) in the general population?

DMBT1 p.Arg562His (c.1685G>A) is rare (popmax 0.114%, sas) (gnomAD).

What do computational predictors say about DMBT1 p.Arg562His (c.1685G>A)?

AlphaMissense predicts likely benign (score 0.1744) — an in-silico prediction, not a clinical call.

DMBT1 p.Arg562His

c.1685G>A · rs373395522 · VCV2361486

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1744 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.114%, sas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1744	likely benign
REVEL	0.014	strongly benign-leaning
SaProt	LLR -11.22	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 -3.7
Regional constraint	o/e 1.17	unconstrained · MANE · 40 kb · p 3.3e-08 · regional, not allelic
Overall
CADD	1.813	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.114% South Asian · 99/86,970 alleles

Filtering AF 0.0956% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0889%

Overall 0.0103% 163/1,588,648 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.114%	878
African / African-American	0.0188%	5,330
Admixed American	0.0168%	5,953
Remaining individualsnot grpmax-eligible	0.0065%	15,386
European (non-Finnish)	0.00309%	32,385

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.Arg562His
Coding: c.1685G>A
MANE Select: NM_001377530
dbSNP: rs373395522
Type: single nucleotide variant
Location: chr10:122586285 (GRCh38)
Gene constraint: LOEUF 0.904 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.29 · 6 PDB
Residue 562: a disulfide bond; the srcr 4 domain

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

Similar variants

DMBT1 p.Arg562Cys Uncertain significance ★ ⚠ 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
DMBT1 p.Asp696= Likely 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-arg562his (accessed [today's date]).

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