Is PGAP1 p.Ser388fs (c.1162_1163del) pathogenic?

PGAP1 p.Ser388fs (c.11621163del) is classified Likely pathogenic in PGAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-04-22). Very rare (popmax 6.53e-05%).

How common is PGAP1 p.Ser388fs (c.1162_1163del) in the general population?

PGAP1 p.Ser388fs (c.1162_1163del) is very rare (popmax 6.53e-05%) (gnomAD).

PGAP1 p.Ser388fs

c.1162_1163del · rs1702072175 · VCV1678377

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 6.53e-05%)

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 10 of 27
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 3.7	GERP 0.66, phastCons 1
Overall
CADD	33.0	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 6.53e-05%

Overall 6.53e-05% 1/1,531,972 alleles · very rare exomes 0/1,379,854 · genomes 1/152,118 · 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.Ser388fs
Coding: c.1162_1163del
MANE Select: NM_024989
dbSNP: rs1702072175
Type: Microsatellite
Location: chr2:196890838 (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.Ile465fs Pathogenic ★★ same type
PGAP1 p.Leu197del Pathogenic/Likely pathogenic ★★ same type
PGAP1 p.Val441del Likely pathogenic ★ same type
PGAP1 c.808-7_808-3del Conflicting classifications of pathogenicity ★ same type
PGAP1 c.1174-20_1174-16del Likely benign ★ same type
PGAP1 c.1350+84CA[3] Benign ★ same type
PGAP1 c.807+173GAAT[6] Benign ★ same type
PGAP1 c.861-14_861-11del Benign ★ 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-p-ser388fs (accessed [today's date]).

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