Is DMP1 p.Gly512Ser (c.1534G>A) pathogenic?

DMP1 p.Gly512Ser (c.1534G>A) is classified Uncertain significance in DMP1 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-04-01). AlphaMissense: likely pathogenic (0.763); Very rare (popmax 0.00167%, amr); Associated with Inborn genetic diseases.

What condition is associated with DMP1 p.Gly512Ser (c.1534G>A)?

DMP1 p.Gly512Ser (c.1534G>A) is associated with Inborn genetic diseases, hypophosphatemic rickets, autosomal recessive, 1 (ClinVar).

How common is DMP1 p.Gly512Ser (c.1534G>A) in the general population?

DMP1 p.Gly512Ser (c.1534G>A) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about DMP1 p.Gly512Ser (c.1534G>A)?

AlphaMissense predicts likely pathogenic (score 0.763) — an in-silico prediction, not a clinical call.

DMP1 p.Gly512Ser

c.1534G>A · rs377414504 · VCV903830

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

AlphaMissense

likely pathogenic

0.763 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.763	likely pathogenic
REVEL	0.348	indeterminate
SaProt	LLR -5.11	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 10	GERP 2.1, phastCons 1
Overall
CADD	24.2	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 0.00167% Admixed American · 1/60,006 alleles

Filtering AF 0.000878% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000717%

Overall 0.00124% 20/1,614,046 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	60,006
European (non-Finnish)	0.00144%	69,413
African / African-American	0.00133%	74,934
South Asian	0.0011%	91,078

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.Gly512Ser
Coding: c.1534G>A
MANE Select: NM_001142327 · reported on NM_004407
dbSNP: rs377414504
Type: single nucleotide variant
Location: chr4:87663312 (GRCh38)
Structure: AlphaFold pLDDT 53.56 · 1 PDB
Residue 512: the 'required for transcriptional activation' 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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: hypophosphatemic rickets, autosomal recessive, 1

Similar variants

DMP1 p.Gly512Cys Uncertain significance ★★ ⚠ same residue
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

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-gly512ser (accessed [today's date]).

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