Is DMP1 p.Ala440Val (c.1319C>T) pathogenic?

DMP1 p.Ala440Val (c.1319C>T) is classified Uncertain significance in DMP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-09-27). AlphaMissense: likely benign (0.1131); Ultra-rare (popmax 0.0164%, mid); Associated with Inborn genetic diseases.

What condition is associated with DMP1 p.Ala440Val (c.1319C>T)?

DMP1 p.Ala440Val (c.1319C>T) is associated with Inborn genetic diseases (ClinVar).

How common is DMP1 p.Ala440Val (c.1319C>T) in the general population?

DMP1 p.Ala440Val (c.1319C>T) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

What do computational predictors say about DMP1 p.Ala440Val (c.1319C>T)?

AlphaMissense predicts likely benign (score 0.1131) — an in-silico prediction, not a clinical call.

DMP1 p.Ala440Val

c.1319C>T · rs985824172 · VCV2367340

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1131 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1131	likely benign
REVEL	0.031	moderately benign-leaning
SaProt	LLR -6.06	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 -0.081	GERP -1.2
Overall
CADD	6.533	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 0.0164% Middle Eastern · 1/6,084 alleles

Filtering AF 0.00623% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00467%

Overall 0.000681% 11/1,614,088 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,084
African / African-American	0.012%	8,326
European (non-Finnish)	8.47e-05%	1,180,052

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.Ala440Val
Coding: c.1319C>T
MANE Select: NM_001142327 · reported on NM_004407
dbSNP: rs985824172
Type: single nucleotide variant
Location: chr4:87663097 (GRCh38)
Structure: AlphaFold pLDDT 53.56 · 1 PDB
Residue 440: 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

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-ala440val (accessed [today's date]).

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