Is ALPL p.Asn302fs (c.903del) pathogenic?

ALPL p.Asn302fs (c.903del) is classified Pathogenic in ALPL (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-08-29). Very rare (popmax 0.0011%, sas); Associated with hypophosphatasia.

What condition is associated with ALPL p.Asn302fs (c.903del)?

ALPL p.Asn302fs (c.903del) is associated with hypophosphatasia, infantile hypophosphatasia (ClinVar).

How common is ALPL p.Asn302fs (c.903del) in the general population?

ALPL p.Asn302fs (c.903del) is very rare (popmax 0.0011%, sas) (gnomAD).

How is Hypophosphatasia inherited?

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

ALPL p.Asn302fs

c.903del · rs768160006 · VCV370761

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Conditions

hypophosphatasia

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 9 of 12
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 3.7	GERP -3.2, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/91,072 alleles

Overall 6.84e-05% 1/1,461,832 alleles · very rare

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: ALPL
Protein: p.Asn302fs
Coding: c.903del
MANE Select: NM_000478
dbSNP: rs768160006
Type: Deletion
Location: chr1:21573704 (GRCh38)
Gene constraint: LOEUF 0.987 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.74 · 5 PDB

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

Also linked: infantile hypophosphatasia

For Hypophosphatasia (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive
Onset: All ages

Similar variants

ALPL p.Asn302Lys Uncertain significance ★★ ⚠ same residue
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.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-asn302fs (accessed [today's date]).

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