Is DMP1 p.Thr143Ile (c.428C>T) pathogenic?

DMP1 p.Thr143Ile (c.428C>T) is classified Uncertain significance in DMP1 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-01-22). AlphaMissense: likely benign (0.1556); Ultra-rare (popmax 0.022%, nfe); Associated with Inborn genetic diseases.

What condition is associated with DMP1 p.Thr143Ile (c.428C>T)?

DMP1 p.Thr143Ile (c.428C>T) is associated with Inborn genetic diseases, hypophosphatemic rickets, autosomal recessive, 1 (ClinVar).

How common is DMP1 p.Thr143Ile (c.428C>T) in the general population?

DMP1 p.Thr143Ile (c.428C>T) is ultra-rare (popmax 0.022%, nfe) (gnomAD).

What do computational predictors say about DMP1 p.Thr143Ile (c.428C>T)?

AlphaMissense predicts likely benign (score 0.1556) — an in-silico prediction, not a clinical call.

DMP1 p.Thr143Ile

c.428C>T · rs370153862 · VCV349973

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.1556 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.022%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1556	likely benign
REVEL	0.031	moderately benign-leaning
SaProt	LLR -7.40	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 -2.3	GERP -3
Overall
CADD	7.204	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 0.022% European (non-Finnish) · 260/1,180,050 alleles

Filtering AF 0.0198% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.019%

Overall 0.0195% 314/1,614,072 alleles · ultra-rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.0484%	2,066
Remaining individualsnot grpmax-eligible	0.032%	3,125
European (non-Finnish)grpmax	0.022%	4,539
Admixed American	0.00167%	60,014
African / African-American	0.00133%	74,914
South Asian	0.0011%	91,090

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Thr143Ile
Coding: c.428C>T
MANE Select: NM_001142327 · reported on NM_004407
dbSNP: rs370153862
Type: single nucleotide variant
Location: chr4:87662206 (GRCh38)
Structure: AlphaFold pLDDT 53.56 · 1 PDB
Residue 143: the 'interaction with ccnd2' region; the 'required for dna-binding' region; the 'required for transcriptional activation' 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.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
DMP1 p.Asn332Lys 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-thr143ile (accessed [today's date]).

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