Is PGAP1 p.Ile895fs (c.2685del) pathogenic?

PGAP1 p.Ile895fs (c.2685del) is classified Uncertain significance in PGAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-10). Associated with intellectual disability, autosomal recessive 42.

What condition is associated with PGAP1 p.Ile895fs (c.2685del)?

PGAP1 p.Ile895fs (c.2685del) is associated with intellectual disability, autosomal recessive 42 (ClinVar).

PGAP1 p.Ile895fs

c.2685del · VCV4879549

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

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	escapes	premature termination codon in the last exon (27 of 27) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.5	GERP 1.7, phastCons 1

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

Variant & gene context

Gene: PGAP1
Protein: p.Ile895fs
Coding: c.2685del
MANE Select: NM_024989
Type: Deletion
Location: chr2:196841318 (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.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.Pro92del Pathogenic ★ same condition
PGAP1 p.Pro92fs Pathogenic ★ same condition
PGAP1 p.Ser97fs Likely 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-ile895fs (accessed [today's date]).

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