Is DMBT1 p.Val1017Met (c.3049G>A) pathogenic?

DMBT1 p.Val1017Met (c.3049G>A) is classified Uncertain significance in DMBT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-01). AlphaMissense: likely pathogenic (0.8333); Rare (popmax 0.599%, sas).

How common is DMBT1 p.Val1017Met (c.3049G>A) in the general population?

DMBT1 p.Val1017Met (c.3049G>A) is rare (popmax 0.599%, sas) (gnomAD).

What do computational predictors say about DMBT1 p.Val1017Met (c.3049G>A)?

AlphaMissense predicts likely pathogenic (score 0.8333) — an in-silico prediction, not a clinical call.

DMBT1 p.Val1017Met

c.3049G>A · VCV4241317

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8333 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.599%, sas)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.8333	likely pathogenic
REVEL	0.429	indeterminate
SaProt	LLR -13.95	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.46	GERP 0.74, phastCons 0.001
Regional constraint	o/e 1.17	unconstrained · MANE · 40 kb · p 3.3e-08 · regional, not allelic
Overall
CADD	23.3	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.599% South Asian · 546/91,080 alleles

Filtering AF 0.558% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.541%

Overall 0.0353% 570/1,613,856 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.599%	167
Remaining individualsnot grpmax-eligible	0.0224%	4,462
Middle Eastern	0.0166%	6,032
East Asian	0.00223%	44,870
European (non-Finnish)	0.000678%	147,473

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.Val1017Met
Coding: c.3049G>A
MANE Select: NM_001377530
Type: single nucleotide variant
Location: chr10:122598866 (GRCh38)
Gene constraint: LOEUF 0.904 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.29 · 6 PDB
Residue 1017: a β-strand; the srcr 8 domain

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-val1017met (accessed [today's date]).

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