Is ALPL p.Asp185_Trp186del (c.553_558del) pathogenic?

ALPL p.Asp185Trp186del (c.553558del) is classified Likely pathogenic in ALPL (ClinVar, Single submitter, 1 submitter; last evaluated 2026-09-01). Associated with hypophosphatasia.

What condition is associated with ALPL p.Asp185_Trp186del (c.553_558del)?

ALPL p.Asp185_Trp186del (c.553_558del) is associated with hypophosphatasia (ClinVar).

How is Hypophosphatasia inherited?

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

ALPL p.Asp185_Trp186del

c.553_558del · VCV4974808

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

Conditions

hypophosphatasia

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 2.8	GERP -0.43, phastCons 1

Variant & gene context

Gene: ALPL
Protein: p.Asp185_Trp186del
Coding: c.553_558del
MANE Select: NM_000478
Type: Deletion
Location: chr1:21564119 (GRCh38)
Gene constraint: LOEUF 0.987 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.74 · 5 PDB
Residue 185: a disulfide bond

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

Disease context

hypophosphatasia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Hypophosphatasia (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive
Onset: All ages

Similar variants

ALPL c.793-30_793-11del Pathogenic/Likely pathogenic ★★ same condition
ALPL p.Ala492fs Pathogenic/Likely pathogenic ★★ same condition
ALPL p.Arg138fs Pathogenic ★★ same condition
ALPL p.Arg272fs Pathogenic/Likely pathogenic ★★ same condition
ALPL p.Asn16fs Pathogenic ★★ same condition
ALPL p.Asn190del Pathogenic/Likely pathogenic ★★ same condition
ALPL p.Asn302fs Pathogenic ★★ same condition
ALPL p.Gln143fs Pathogenic ★★ 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/alpl-p-asp185-trp186del (accessed [today's date]).

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