Is PGAP1 p.Pro92fs (c.275del) pathogenic?

PGAP1 p.Pro92fs (c.275del) is classified Pathogenic in PGAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-27). Very rare (popmax 0.00017%, nfe); Associated with intellectual disability, autosomal recessive 42.

What condition is associated with PGAP1 p.Pro92fs (c.275del)?

PGAP1 p.Pro92fs (c.275del) is associated with intellectual disability, autosomal recessive 42 (ClinVar).

How common is PGAP1 p.Pro92fs (c.275del) in the general population?

PGAP1 p.Pro92fs (c.275del) is very rare (popmax 0.00017%, nfe) (gnomAD).

PGAP1 p.Pro92fs

c.275del · rs2468726625 · VCV2023072

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00017%, nfe)

Conditions

intellectual disability, autosomal recessive 42

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 2 of 27
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.1	GERP -0.71, phastCons 0.99

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00017% European (non-Finnish) · 2/1,178,950 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000124% 2/1,611,184 alleles · very rare exomes 2/1,458,892 · genomes 0/152,292 · joint denominator

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: PGAP1
Protein: p.Pro92fs
Coding: c.275del
MANE Select: NM_024989
dbSNP: rs2468726625
Type: Deletion
Location: chr2:196920023 (GRCh38)
Gene constraint: LOEUF 0.691 · pLI 0.02 (gnomAD)
Structure: AlphaFold pLDDT 89.15

Full PGAP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

intellectual disability, autosomal recessive 42 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PGAP1 p.Pro92del Pathogenic ★ same residue
PGAP1 p.Leu681fs Pathogenic/Likely pathogenic ★★ same condition
PGAP1 c.1426+1del Likely pathogenic ★ same condition
PGAP1 p.Asn7fs Pathogenic ★ same condition
PGAP1 p.Cys623fs Pathogenic ★ same condition
PGAP1 p.Lys308fs Pathogenic ★ same condition
PGAP1 p.Ser97fs Likely pathogenic ★ same condition
PGAP1 p.Val516fs 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/pgap1-p-pro92fs (accessed [today's date]).

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