Is DMP1 p.Gln159Lys (c.475C>A) pathogenic?

DMP1 p.Gln159Lys (c.475C>A) is classified Benign in DMP1 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-02-02). AlphaMissense: likely benign (0.0724); Common (popmax 5.75%, amr) — too common for a highly-penetrant pathogenic allele; Associated with hypophosphatemic rickets, autosomal recessive, 1.

What condition is associated with DMP1 p.Gln159Lys (c.475C>A)?

DMP1 p.Gln159Lys (c.475C>A) is associated with hypophosphatemic rickets, autosomal recessive, 1 (ClinVar).

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.Gln159Lys (c.475C>A)?

AlphaMissense predicts likely benign (score 0.0724) — an in-silico prediction, not a clinical call.

DMP1 p.Gln159Lys

Q: How common is DMP1 p.Gln159Lys (c.475C>A) in the general population?

DMP1 p.Gln159Lys (c.475C>A) is common (popmax 5.75%, amr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.475C>A · rs79402270 · VCV349974

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.0724 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 5.75%, amr) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hypophosphatemic rickets, autosomal recessive, 1

Computational evidence

Protein change
AlphaMissense	0.0724	likely benign
REVEL	0.077	moderately benign-leaning
SaProt	LLR -6.42	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 1.3	GERP 0.077, phastCons 0.001
Overall
CADD	18.44	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 5.75% Admixed American · 3,448/60,014 alleles

Filtering AF 5.59% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.52%

Overall 0.543% 8,764/1,614,116 alleles · common

Ancestry group	Frequency	1 in
Admixed Americangrpmax	5.75%	17
East Asian	5.62%	18
Ashkenazi Jewishnot grpmax-eligible	0.544%	184
Remaining individualsnot grpmax-eligible	0.437%	229
European (non-Finnish)	0.185%	541
South Asian	0.0988%	1,012
African / African-American	0.0693%	1,443
Finnishnot grpmax-eligible	0.0547%	1,829
Middle Eastern	0.033%	3,031

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.Gln159Lys
Coding: c.475C>A
MANE Select: NM_001142327 · reported on NM_004407
dbSNP: rs79402270
Type: single nucleotide variant
Location: chr4:87662253 (GRCh38)
Structure: AlphaFold pLDDT 53.56 · 1 PDB
Residue 159: 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

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-gln159lys (accessed [today's date]).

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