Is DMP1 p.Ser341= (c.1023C>T) pathogenic?

DMP1 p.Ser341= (c.1023C>T) is classified Conflicting classifications of pathogenicity in DMP1 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-12-24). Ultra-rare (popmax 0.0825%, mid); Associated with hypophosphatemic rickets, autosomal recessive, 1.

What condition is associated with DMP1 p.Ser341= (c.1023C>T)?

DMP1 p.Ser341= (c.1023C>T) is associated with hypophosphatemic rickets, autosomal recessive, 1 (ClinVar).

How common is DMP1 p.Ser341= (c.1023C>T) in the general population?

DMP1 p.Ser341= (c.1023C>T) is ultra-rare (popmax 0.0825%, 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.Ser341=

c.1023C>T · rs140807822 · VCV349981

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0825%, mid)

Conditions

hypophosphatemic rickets, autosomal recessive, 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2.4	GERP -3.6
Overall
CADD	0.303	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0825% Middle Eastern · 5/6,060 alleles

Filtering AF 0.0324% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.021%

Overall 0.0464% 748/1,612,756 alleles · ultra-rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	1.67%	60
Remaining individualsnot grpmax-eligible	0.154%	650
Middle Easterngrpmax	0.0825%	1,212
Admixed American	0.0184%	5,449
European (non-Finnish)	0.0118%	8,482
African / African-American	0.00267%	37,471

Ashkenazi Jewish 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.Ser341=
Coding: c.1023C>T
MANE Select: NM_001142327 · reported on NM_004407
dbSNP: rs140807822
Type: single nucleotide variant
Location: chr4:87662801 (GRCh38)
Structure: AlphaFold pLDDT 53.56 · 1 PDB
Residue 341: the myb-like 2 domain; the 'required for dna-binding' region; the 'interaction with ccnd1, ccnd2 and ccnd3' 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.Gly135Ter Pathogenic/Likely pathogenic ★★ same condition
DMP1 p.Met1Val 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
DMP1 p.Asn332Lys 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-ser341 (accessed [today's date]).

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