Is DMBT1 p.Ala543Val (c.1628C>T) pathogenic?

DMBT1 p.Ala543Val (c.1628C>T) is classified Uncertain significance in DMBT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-23). AlphaMissense: ambiguous (0.4823); Very rare (popmax 0.00168%, amr).

How common is DMBT1 p.Ala543Val (c.1628C>T) in the general population?

DMBT1 p.Ala543Val (c.1628C>T) is very rare (popmax 0.00168%, amr) (gnomAD).

What do computational predictors say about DMBT1 p.Ala543Val (c.1628C>T)?

AlphaMissense predicts ambiguous (score 0.4823) — an in-silico prediction, not a clinical call.

DMBT1 p.Ala543Val

c.1628C>T · rs2097788170 · VCV2488665

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4823 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00168%, amr)

Computational evidence

Protein change
AlphaMissense	0.4823	ambiguous
REVEL	0.367	indeterminate
SaProt	LLR -11.44	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.2	GERP 1.8, phastCons 0.61
Regional constraint	o/e 1.17	unconstrained · MANE · 40 kb · p 3.3e-08 · regional, not allelic
Overall
CADD	18.26	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 0.00168% Admixed American · 1/59,556 alleles

Overall 6.94e-05% 1/1,440,114 alleles · very rare

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.Ala543Val
Coding: c.1628C>T
MANE Select: NM_001377530
dbSNP: rs2097788170
Type: single nucleotide variant
Location: chr10:122586228 (GRCh38)
Gene constraint: LOEUF 0.904 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.29 · 6 PDB
Residue 543: 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.Ala543Pro 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-ala543val (accessed [today's date]).

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