Is DMP1 p.Arg272Cys (c.814C>T) pathogenic?

DMP1 p.Arg272Cys (c.814C>T) is classified Uncertain significance in DMP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-08). AlphaMissense: likely benign (0.1865); Ultra-rare (popmax 0.0156%, eas).

How common is DMP1 p.Arg272Cys (c.814C>T) in the general population?

DMP1 p.Arg272Cys (c.814C>T) is ultra-rare (popmax 0.0156%, eas) (gnomAD).

What do computational predictors say about DMP1 p.Arg272Cys (c.814C>T)?

AlphaMissense predicts likely benign (score 0.1865) — an in-silico prediction, not a clinical call.

DMP1 p.Arg272Cys

c.814C>T · rs373457215 · VCV2140140

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1865 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0156%, eas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1865	likely benign
REVEL	0.17	moderately benign-leaning
SaProt	LLR -10.55	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.2	GERP 1.7, phastCons 0.01
Overall
CADD	23.3	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 0.0156% East Asian · 7/44,880 alleles

Filtering AF 0.00726% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00515%

Overall 0.00112% 18/1,613,940 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0156%	6,411
African / African-American	0.00801%	12,486
Admixed American	0.00167%	59,994
Remaining individualsnot grpmax-eligible	0.0016%	62,486
European (non-Finnish)	0.000254%	393,338

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.Arg272Cys
Coding: c.814C>T
MANE Select: NM_001142327 · reported on NM_004407
dbSNP: rs373457215
Type: single nucleotide variant
Location: chr4:87662592 (GRCh38)
Structure: AlphaFold pLDDT 53.56 · 1 PDB
Residue 272: the hth myb-type domain; the 'required for dna-binding' region; the 'interaction with ccnd1, ccnd2 and ccnd3' region

Full DMP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DMP1 p.Arg272His Conflicting classifications of pathogenicity ★ ⚠ same residue
DMP1 p.Gly135Ter Pathogenic/Likely pathogenic ★★ same type
DMP1 p.Met1Val Pathogenic/Likely pathogenic ★★ same type
DMP1 c.*159T>A Uncertain significance ★★ same type
DMP1 c.*77T>C Uncertain significance ★★ same type
DMP1 p.Arg173Trp Uncertain significance ★★ ⚠ same type
DMP1 p.Arg302Ile Uncertain significance ★★ ⚠ same type
DMP1 p.Arg310Lys Uncertain significance ★★ ⚠ same type

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-arg272cys (accessed [today's date]).

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