Is DMP1 p.Lys124Gln (c.370A>C) pathogenic?

DMP1 p.Lys124Gln (c.370A>C) is classified Uncertain significance in DMP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-12). AlphaMissense: likely benign (0.0987); Very rare (popmax 0.00186%, nfe); Associated with hypophosphatemic rickets, autosomal recessive, 1.

What condition is associated with DMP1 p.Lys124Gln (c.370A>C)?

DMP1 p.Lys124Gln (c.370A>C) is associated with hypophosphatemic rickets, autosomal recessive, 1 (ClinVar).

How common is DMP1 p.Lys124Gln (c.370A>C) in the general population?

DMP1 p.Lys124Gln (c.370A>C) is very rare (popmax 0.00186%, nfe) (gnomAD).

How is Autosomal recessive hypophosphatemic rickets inherited?

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

What do computational predictors say about DMP1 p.Lys124Gln (c.370A>C)?

AlphaMissense predicts likely benign (score 0.0987) — an in-silico prediction, not a clinical call.

DMP1 p.Lys124Gln

c.370A>C · rs886059686 · VCV349972

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0987 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00186%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hypophosphatemic rickets, autosomal recessive, 1

Computational evidence

Protein change
AlphaMissense	0.0987	likely benign
REVEL	0.013	strongly benign-leaning
SaProt	LLR -5.62	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.1	GERP -2, phastCons 1
Overall
CADD	12.7	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 0.00186% European (non-Finnish) · 22/1,180,048 alleles

Filtering AF 0.00122% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.00136% 22/1,614,128 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.Lys124Gln
Coding: c.370A>C
MANE Select: NM_004407
dbSNP: rs886059686
Type: single nucleotide variant
Location: chr4:87662148 (GRCh38)
Gene constraint: LOEUF 1.209 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 47.80
Residue 124: the 'disordered' 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-lys124gln (accessed [today's date]).

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