Is PGAP3 p.Ala15fs (c.43dup) pathogenic?

PGAP3 p.Ala15fs (c.43dup) is classified Likely pathogenic in PGAP3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-01). No allele count reported in gnomAD v4.1 (AN 1,465,072); Associated with hyperphosphatasia-intellectual disability syndrome.

What condition is associated with PGAP3 p.Ala15fs (c.43dup)?

PGAP3 p.Ala15fs (c.43dup) is associated with hyperphosphatasia-intellectual disability syndrome (ClinVar).

How common is PGAP3 p.Ala15fs (c.43dup) in the general population?

PGAP3 p.Ala15fs (c.43dup) is no allele count reported in gnomAD v4.1 (AN 1,465,072) (gnomAD).

PGAP3 p.Ala15fs

Q: How is Hyperphosphatasia-intellectual disability syndrome inherited?

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

c.43dup · rs765928877 · VCV3068561

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,465,072)

Conditions

hyperphosphatasia-intellectual disability syndrome

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 1 of 8
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 6.4	GERP 1.4, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,465,072). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: PGAP3
Protein: p.Ala15fs
Coding: c.43dup
MANE Select: NM_033419
dbSNP: rs765928877
Type: Duplication
Location: chr17:39687971 (GRCh38)
Gene constraint: LOEUF 1.147 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 93.17

Full PGAP3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

hyperphosphatasia-intellectual disability syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Hyperphosphatasia-intellectual disability syndrome (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

PGAP3 p.Met135fs Pathogenic ★★ same type
PGAP3 p.Trp152fs Pathogenic ★★ same type
PGAP3 p.Cys68fs Likely pathogenic ★ same type
PGAP3 p.Phe151fs Pathogenic ★ same type
PGAP3 p.Ser300fs Likely pathogenic ★ same type
PGAP3 p.Val28fs Pathogenic ★ same type
PGAP3 c.279+4_279+7dup Likely benign ★ same type
PGAP3 c.433-8dup Likely benign ★ same type

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/pgap3-p-ala15fs (accessed [today's date]).

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