Is PGAP1 p.Arg786fs (c.2357_2358insTA) pathogenic?

PGAP1 p.Arg786fs (c.23572358insTA) is classified Pathogenic in PGAP1 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2023-02-02). Very rare (popmax 0.00269%, afr); Associated with Inborn genetic diseases.

What condition is associated with PGAP1 p.Arg786fs (c.2357_2358insTA)?

PGAP1 p.Arg786fs (c.2357_2358insTA) is associated with Inborn genetic diseases, intellectual disability, autosomal recessive 42 (ClinVar).

How common is PGAP1 p.Arg786fs (c.2357_2358insTA) in the general population?

PGAP1 p.Arg786fs (c.2357_2358insTA) is very rare (popmax 0.00269%, afr) (gnomAD).

PGAP1 p.Arg786fs

c.2357_2358insTA · rs767774867 · VCV503954

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00269%, afr)

Conditions

Inborn genetic diseases

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 25 of 27
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 2	GERP 0.56, phastCons 1
Overall
CADD	34.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00269% African / African-American · 2/74,360 alleles

Filtering AF 0.00148% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00125%

Overall 0.0017% 27/1,586,110 alleles · very rare exomes 26/1,433,944 · genomes 1/152,166 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00269%	37,180
European (non-Finnish)	0.00215%	46,491

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.Arg786fs
Coding: c.2357_2358insTA
MANE Select: NM_024989
dbSNP: rs767774867
Type: Insertion
Location: chr2:196844055 (GRCh38)
Gene constraint: LOEUF 0.691 · pLI 0.02 (gnomAD)
Structure: AlphaFold pLDDT 89.15
Residue 786: the 'disordered' region

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: intellectual disability, autosomal recessive 42

Similar variants

PGAP1 c.1350+4_1350+5insAAA Uncertain significance ★ same condition
PGAP1 c.2150+9_2150+10insA Likely benign ★ same condition
PGAP1 p.Gln466Ter Pathogenic ★★ same condition
PGAP1 p.Gln555Ter Pathogenic/Likely pathogenic ★★ same condition
PGAP1 p.Ile465fs Pathogenic ★★ same condition
PGAP1 p.Leu197del Pathogenic/Likely pathogenic ★★ same condition
PGAP1 p.Leu681fs Pathogenic/Likely pathogenic ★★ same condition
PGAP1 p.Tyr758Ter Pathogenic/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-arg786fs (accessed [today's date]).

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