Is ALPL p.Val161fs (c.480del) pathogenic?

ALPL p.Val161fs (c.480del) is classified Pathogenic in ALPL (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-09-01). Very rare (popmax 0.000508%, nfe); Associated with Inborn genetic diseases.

What condition is associated with ALPL p.Val161fs (c.480del)?

ALPL p.Val161fs (c.480del) is associated with Inborn genetic diseases, hypophosphatasia, adult hypophosphatasia (ClinVar).

How common is ALPL p.Val161fs (c.480del) in the general population?

ALPL p.Val161fs (c.480del) is very rare (popmax 0.000508%, nfe) (gnomAD).

ALPL p.Val161fs

c.480del · rs1644527306 · VCV1355608

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000508%, nfe)

Conditions

Inborn genetic diseases

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 6 of 12
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.7	GERP 1.9, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000508% European (non-Finnish) · 6/1,179,980 alleles

Filtering AF 0.000183% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00012%

Overall 0.000411% 6/1,461,604 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.Val161fs
Coding: c.480del
MANE Select: NM_000478
dbSNP: rs1644527306
Type: Deletion
Location: chr1:21564048 (GRCh38)
Gene constraint: LOEUF 0.987 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.74 · 5 PDB
Residue 161: a β-strand; a disulfide bond

Full ALPL 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: hypophosphatasia adult hypophosphatasia

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-val161fs (accessed [today's date]).

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