Is DMP1 p.Ser57Arg (c.171C>G) pathogenic?

DMP1 p.Ser57Arg (c.171C>G) is classified Uncertain significance in DMP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-27). AlphaMissense: ambiguous (0.542); Very rare (popmax 0.00223%, eas); Associated with Inborn genetic diseases.

What condition is associated with DMP1 p.Ser57Arg (c.171C>G)?

DMP1 p.Ser57Arg (c.171C>G) is associated with Inborn genetic diseases (ClinVar).

How common is DMP1 p.Ser57Arg (c.171C>G) in the general population?

DMP1 p.Ser57Arg (c.171C>G) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about DMP1 p.Ser57Arg (c.171C>G)?

AlphaMissense predicts ambiguous (score 0.542) — an in-silico prediction, not a clinical call.

DMP1 p.Ser57Arg

c.171C>G · rs764786698 · VCV3083094

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.542 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.542	ambiguous
REVEL	0.175	moderately benign-leaning
SaProt	LLR -9.39	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	Δ0.33	acceptor loss, 35 bp away · masked 0 · deltas
Pangolin	Δ0.31	loss · gain 0.02 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 4.9	GERP 0.99, phastCons 1
Overall
CADD	22.4	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 0.00223% East Asian · 1/44,868 alleles

Overall 0.000657% 1/152,158 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.Ser57Arg
Coding: c.171C>G
MANE Select: NM_001142327 · reported on NM_004407
dbSNP: rs764786698
Type: single nucleotide variant
Location: chr4:87659466 (GRCh38)
Structure: AlphaFold pLDDT 53.56 · 1 PDB
Residue 57: the 'interaction with ccnd2' 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

Similar variants

DMP1 p.Arg302Ile Uncertain significance ★★ ⚠ same condition
DMP1 p.Asn233Lys Uncertain significance ★★ ⚠ same condition
DMP1 p.Asp453Asn Uncertain significance ★★ ⚠ same condition
DMP1 p.Glu385Lys Uncertain significance ★★ ⚠ same condition
DMP1 p.Glu398Gly Uncertain significance ★★ ⚠ same condition
DMP1 p.Glu470Lys Uncertain significance ★★ ⚠ same condition
DMP1 p.Gly207Ser Uncertain significance ★★ ⚠ same condition
DMP1 p.Gly512Cys 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-ser57arg (accessed [today's date]).

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