Is PGAP1 p.Val516fs (c.1546_1549del) pathogenic?

PGAP1 p.Val516fs (c.15461549del) is classified Pathogenic in PGAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-14). Very rare (popmax 6.22e-05%); Associated with intellectual disability, autosomal recessive 42.

What condition is associated with PGAP1 p.Val516fs (c.1546_1549del)?

PGAP1 p.Val516fs (c.1546_1549del) is associated with intellectual disability, autosomal recessive 42 (ClinVar).

How common is PGAP1 p.Val516fs (c.1546_1549del) in the general population?

PGAP1 p.Val516fs (c.1546_1549del) is very rare (popmax 6.22e-05%) (gnomAD).

PGAP1 p.Val516fs

c.1546_1549del · rs1559346318 · VCV3235692

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 6.22e-05%)

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 16 of 27
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.4	GERP -0.6, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.22e-05%

Overall 6.22e-05% 1/1,607,040 alleles · very rare exomes 1/1,454,776 · genomes 0/152,264 · 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.Val516fs
Coding: c.1546_1549del
MANE Select: NM_024989
dbSNP: rs1559346318
Type: Deletion
Location: chr2:196873531 (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-val516fs (accessed [today's date]).

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