Is DMP1 p.Met1Val (c.1A>G) pathogenic?

DMP1 p.Met1Val (c.1A>G) is classified Pathogenic/Likely pathogenic in DMP1 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-03-05). Ultra-rare (popmax 0.0496%, mid); Associated with hypophosphatemic rickets, autosomal recessive, 1.

What condition is associated with DMP1 p.Met1Val (c.1A>G)?

DMP1 p.Met1Val (c.1A>G) is associated with hypophosphatemic rickets, autosomal recessive, 1 (ClinVar).

How common is DMP1 p.Met1Val (c.1A>G) in the general population?

DMP1 p.Met1Val (c.1A>G) is ultra-rare (popmax 0.0496%, mid) (gnomAD).

How is Autosomal recessive hypophosphatemic rickets inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

DMP1 p.Met1Val

c.1A>G · rs104893834 · VCV8575

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

Consequence

start-loss

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0496%, mid)

Conditions

hypophosphatemic rickets, autosomal recessive, 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	start-loss	predicted loss-of-function
REVEL	0.299	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8	GERP 0.45, phastCons 1
Overall
CADD	21.5	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 0.0496% Middle Eastern · 3/6,050 alleles

Filtering AF 0.0134% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00719%

Overall 0.000344% 5/1,453,326 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0496%	2,017
European (non-Finnish)	0.000171%	586,177

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.Met1Val
Coding: c.1A>G
MANE Select: NM_001142327 · reported on NM_004407
dbSNP: rs104893834
Type: single nucleotide variant
Location: chr4:87656493 (GRCh38)
Structure: AlphaFold pLDDT 53.56 · 1 PDB
Residue 1: the 'interaction with ccnd2' region

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

Disease context

hypophosphatemic rickets, autosomal recessive, 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Autosomal recessive hypophosphatemic rickets (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood, Infancy

Similar variants

DMP1 p.Met1Leu Pathogenic ★ same residue
DMP1 p.Met1Lys Pathogenic ★ same residue
DMP1 p.Gly135Ter Pathogenic/Likely pathogenic ★★ same condition
DMP1 c.*159T>A Uncertain significance ★★ same condition
DMP1 c.*77T>C Uncertain significance ★★ same condition
DMP1 p.Arg173Trp Uncertain significance ★★ ⚠ same condition
DMP1 p.Arg302Ile Uncertain significance ★★ ⚠ same condition
DMP1 p.Asn233Lys Uncertain significance ★★ ⚠ same condition

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-met1val (accessed [today's date]).

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