Is DMP1 p.Ser136Gly (c.406A>G) pathogenic?

DMP1 p.Ser136Gly (c.406A>G) is classified Uncertain significance in DMP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-22). AlphaMissense: likely benign (0.0829); Very rare (popmax 0.00133%, afr); Associated with hypophosphatemic rickets, autosomal recessive, 1.

What condition is associated with DMP1 p.Ser136Gly (c.406A>G)?

DMP1 p.Ser136Gly (c.406A>G) is associated with hypophosphatemic rickets, autosomal recessive, 1 (ClinVar).

How common is DMP1 p.Ser136Gly (c.406A>G) in the general population?

DMP1 p.Ser136Gly (c.406A>G) is very rare (popmax 0.00133%, afr) (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.Ser136Gly (c.406A>G)?

AlphaMissense predicts likely benign (score 0.0829) — an in-silico prediction, not a clinical call.

DMP1 p.Ser136Gly

c.406A>G · VCV3591293

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0829 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hypophosphatemic rickets, autosomal recessive, 1

Computational evidence

Protein change
AlphaMissense	0.0829	likely benign
REVEL	0.051	moderately benign-leaning
SaProt	LLR -7.36	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 3.8	GERP 1.4, phastCons 0.99
Overall
CADD	13.04	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 0.00133% African / African-American · 1/75,054 alleles

Overall 0.000137% 2/1,461,892 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00133%	75,054
European (non-Finnish)	8.47e-05%	1,180,054

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.Ser136Gly
Coding: c.406A>G
Type: single nucleotide variant
Location: chr4:87662184 (GRCh38)

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

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-ser136gly (accessed [today's date]).

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