Is PGAP1 c.2286+293del pathogenic?

PGAP1 c.2286+293del is classified Likely benign in PGAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-08-06). Low-frequency (popmax 2.67%, nfe).

How common is PGAP1 c.2286+293del in the general population?

PGAP1 c.2286+293del is low-frequency (popmax 2.67%, nfe) (gnomAD).

PGAP1 c.2286+293del

rs201051791 · VCV1193339

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

low-frequency (popmax 2.67%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
Splice region	donor +293	deep intronic (+293 nt into the intron)
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.7	GERP -0.85, phastCons 0.03
Overall
CADD	1.706	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 2.67% European (non-Finnish) · 1,718/64,230 alleles

Filtering AF 2.57% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.53%

Overall 2.01% 2,827/140,542 alleles · low-frequency

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	6.51%	15
European (non-Finnish)grpmax	2.67%	37
Remaining individualsnot grpmax-eligible	2.37%	42
Middle Eastern	1.46%	69
Admixed American	1.31%	76
Ashkenazi Jewishnot grpmax-eligible	0.996%	100
African / African-American	0.733%	136
South Asian	0.557%	179
East Asian	0.0811%	1,233

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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
Coding: c.2286+293del
MANE Select: NM_024989
dbSNP: rs201051791
Type: Deletion
Location: chr2:196845589 (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

Similar variants

PGAP1 p.Leu681fs Pathogenic/Likely pathogenic ★★ same type
PGAP1 c.1089+5del Likely pathogenic ★ same type
PGAP1 c.1426+1del Likely pathogenic ★ same type
PGAP1 p.Asn223fs Pathogenic ★ same type
PGAP1 p.Asn7fs Pathogenic ★ same type
PGAP1 p.Asp192fs Likely pathogenic ★ same type
PGAP1 p.Cys623fs Pathogenic ★ same type
PGAP1 p.Lys308fs Pathogenic ★ 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/pgap1-c-2286-plus-293del (accessed [today's date]).

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