Is DMP1 p.Pro419Leu (c.1256C>T) pathogenic?

DMP1 p.Pro419Leu (c.1256C>T) is classified Uncertain significance in DMP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-06). AlphaMissense: likely benign (0.0801); Ultra-rare (popmax 0.024%, afr).

How common is DMP1 p.Pro419Leu (c.1256C>T) in the general population?

DMP1 p.Pro419Leu (c.1256C>T) is ultra-rare (popmax 0.024%, afr) (gnomAD).

What do computational predictors say about DMP1 p.Pro419Leu (c.1256C>T)?

AlphaMissense predicts likely benign (score 0.0801) — an in-silico prediction, not a clinical call.

DMP1 p.Pro419Leu

c.1256C>T · rs145278609 · VCV1016832

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0801 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.024%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0801	likely benign
REVEL	0.06	moderately benign-leaning
SaProt	LLR -6.47	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 -1.1	GERP -0.007
Overall
CADD	9.645	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 0.024% African / African-American · 18/74,918 alleles

Filtering AF 0.0155% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0128%

Overall 0.00409% 66/1,614,012 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.024%	4,162
Remaining individualsnot grpmax-eligible	0.0224%	4,463
European (non-Finnish)	0.0028%	35,758
South Asian	0.0011%	91,080

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.Pro419Leu
Coding: c.1256C>T
MANE Select: NM_001142327 · reported on NM_004407
dbSNP: rs145278609
Type: single nucleotide variant
Location: chr4:87663034 (GRCh38)
Structure: AlphaFold pLDDT 53.56 · 1 PDB
Residue 419: the 'required for dna-binding' region; the 'interaction with ccnd1, ccnd2 and ccnd3' region; the 'disordered' region

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

Similar variants

DMP1 p.Pro419Ser Conflicting classifications of pathogenicity ★ ⚠ same residue
DMP1 p.Pro419= Likely benign ★ 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

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-pro419leu (accessed [today's date]).

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