Is DMP1 p.Ser92fs (c.273del) pathogenic?

DMP1 p.Ser92fs (c.273del) is classified Pathogenic in DMP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-19). Very rare (popmax 0.000678%, nfe).

How common is DMP1 p.Ser92fs (c.273del) in the general population?

DMP1 p.Ser92fs (c.273del) is very rare (popmax 0.000678%, nfe) (gnomAD).

DMP1 p.Ser92fs

c.273del · VCV4732576

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000678%, 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 2.7	GERP 0.33, phastCons 0.16

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000678% European (non-Finnish) · 8/1,180,020 alleles

Filtering AF 0.000292% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000211%

Overall 0.000547% 8/1,461,890 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: DMP1
Protein: p.Ser92fs
Coding: c.273del
MANE Select: NM_001142327 · reported on NM_004407
Type: Deletion
Location: chr4:87662051 (GRCh38)
Structure: AlphaFold pLDDT 53.56 · 1 PDB
Residue 92: the 'interaction with ccnd2' region; the 'required for dna-binding' region; the 'required for transcriptional activation' region

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

Similar variants

DMTF1 p.Thr92Ser Uncertain significance ★ ⚠ same residue
DMP1 p.Glu179fs Likely pathogenic ★ same type
DMP1 p.Ile501fs Uncertain significance ★ 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-ser92fs (accessed [today's date]).

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