Is DMP1 p.Ile501fs (c.1500del) pathogenic?

DMP1 p.Ile501fs (c.1500del) is classified Uncertain significance in DMP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-28). Very rare (popmax 8.47e-05%, nfe).

How common is DMP1 p.Ile501fs (c.1500del) in the general population?

DMP1 p.Ile501fs (c.1500del) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

DMP1 p.Ile501fs

c.1500del · VCV3692121

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function; NMD-escape possible for C-terminal truncations
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.87	GERP -3.9, phastCons 0.98
Overall
CADD	33.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,180,046 alleles

Overall 0.00112% 18/1,614,132 alleles · very rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.0265%	3,767
European (non-Finnish)grpmax	8.47e-05%	1,180,045

Finnish 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: DMP1
Protein: p.Ile501fs
Coding: c.1500del
MANE Select: NM_001142327 · reported on NM_004407
Type: Deletion
Location: chr4:87663276 (GRCh38)
Structure: AlphaFold pLDDT 53.56 · 1 PDB
Residue 501: the 'required for transcriptional activation' region; the 'interaction with ccnd1, ccnd2 and ccnd3' region

Full DMP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DMP1 p.Ile501Phe Uncertain significance ★ ⚠ same residue
DMP1 p.Glu179fs Likely pathogenic ★ same type
DMP1 p.Ser92fs Pathogenic ★ same type
DMTF1 p.Thr534fs Uncertain significance ★ same type
DMP1 c.135+12del Likely benign ★ same type
DMP1 c.55-13del 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/dmp1-p-ile501fs (accessed [today's date]).

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