Is DMP1 p.Ser242Pro (c.724T>C) pathogenic?

DMP1 p.Ser242Pro (c.724T>C) is classified Likely benign in DMP1 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-12-20). AlphaMissense: likely benign (0.1133); Rare (popmax 0.284%, afr); Associated with hypophosphatemic rickets, autosomal recessive, 1.

What condition is associated with DMP1 p.Ser242Pro (c.724T>C)?

DMP1 p.Ser242Pro (c.724T>C) is associated with hypophosphatemic rickets, autosomal recessive, 1 (ClinVar).

How common is DMP1 p.Ser242Pro (c.724T>C) in the general population?

DMP1 p.Ser242Pro (c.724T>C) is rare (popmax 0.284%, afr) (gnomAD).

How is Autosomal recessive hypophosphatemic rickets inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about DMP1 p.Ser242Pro (c.724T>C)?

AlphaMissense predicts likely benign (score 0.1133) — an in-silico prediction, not a clinical call.

DMP1 p.Ser242Pro

c.724T>C · rs147552663 · VCV905667

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.1133 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.284%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hypophosphatemic rickets, autosomal recessive, 1

Computational evidence

Protein change
AlphaMissense	0.1133	likely benign
REVEL	0.076	moderately benign-leaning
SaProt	LLR -9.04	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 1.8	GERP -2.2, phastCons 0.022
Overall
CADD	18.46	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 0.284% African / African-American · 213/74,998 alleles

Filtering AF 0.253% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.241%

Overall 0.0142% 230/1,614,038 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.284%	352
Remaining individualsnot grpmax-eligible	0.0176%	5,682
Admixed American	0.005%	20,005
South Asian	0.0011%	91,072
European (non-Finnish)	0.000169%	590,002

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.Ser242Pro
Coding: c.724T>C
MANE Select: NM_001142327 · reported on NM_004407
dbSNP: rs147552663
Type: single nucleotide variant
Location: chr4:87662502 (GRCh38)
Structure: AlphaFold pLDDT 53.56 · 1 PDB
Residue 242: the myb-like 1 domain; an α-helix; 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

hypophosphatemic rickets, autosomal recessive, 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Autosomal recessive hypophosphatemic rickets (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood, Infancy

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-ser242pro (accessed [today's date]).

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