Is PGAP1 p.Gln555Ter (c.1663C>T) pathogenic?

PGAP1 p.Gln555Ter (c.1663C>T) is classified Pathogenic/Likely pathogenic in PGAP1 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-12-10). Very rare (popmax 0.00102%, nfe); Associated with PGAP1-related disorders.

What condition is associated with PGAP1 p.Gln555Ter (c.1663C>T)?

PGAP1 p.Gln555Ter (c.1663C>T) is associated with PGAP1-related disorders, intellectual disability, autosomal recessive 42 (ClinVar).

How common is PGAP1 p.Gln555Ter (c.1663C>T) in the general population?

PGAP1 p.Gln555Ter (c.1663C>T) is very rare (popmax 0.00102%, nfe) (gnomAD).

PGAP1 p.Gln555Ter

c.1663C>T · rs755341613 · VCV1032203

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00102%, nfe)

Conditions

PGAP1-related disorders

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 18 of 27
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Pangolin	Δ0.48	loss · gain 0.05 · SpliceAI below 0.2 · independent
Constraint at this position
Conservation	phyloP 12	GERP 1.5, phastCons 1
Overall
CADD	38.0	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 0.00102% European (non-Finnish) · 12/1,179,310 alleles

Filtering AF 0.000543% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000429%

Overall 0.000744% 12/1,613,162 alleles · very rare exomes 11/1,460,974 · genomes 1/152,188 · 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.Gln555Ter
Coding: c.1663C>T
MANE Select: NM_024989
dbSNP: rs755341613
Type: single nucleotide variant
Location: chr2:196872506 (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

PGAP1-related disorders

Also linked: intellectual disability, autosomal recessive 42

Similar variants

PGAP1 p.Gln466Ter Pathogenic ★★ same condition
PGAP1 p.Tyr758Ter Pathogenic/Likely pathogenic ★★ same condition
PGAP1 p.Ala298Thr Uncertain significance ★★ ⚠ same condition
PGAP1 p.Ala714Val Uncertain significance ★★ ⚠ same condition
PGAP1 p.Arg231Gln Uncertain significance ★★ ⚠ same condition
PGAP1 p.Arg250His Uncertain significance ★★ ⚠ same condition
PGAP1 p.Arg803Cys Uncertain significance ★★ ⚠ same condition
PGAP1 p.Arg803His Uncertain significance ★★ ⚠ 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-gln555ter (accessed [today's date]).

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