Is PGAP1 p.Cys623Ter (c.1869C>A) pathogenic?

PGAP1 p.Cys623Ter (c.1869C>A) is classified Pathogenic in PGAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-26). No allele count reported in gnomAD v4.1 (AN 1,594,858); Associated with intellectual disability, autosomal recessive 42.

What condition is associated with PGAP1 p.Cys623Ter (c.1869C>A)?

PGAP1 p.Cys623Ter (c.1869C>A) is associated with intellectual disability, autosomal recessive 42 (ClinVar).

How common is PGAP1 p.Cys623Ter (c.1869C>A) in the general population?

PGAP1 p.Cys623Ter (c.1869C>A) is no allele count reported in gnomAD v4.1 (AN 1,594,858) (gnomAD).

PGAP1 p.Cys623Ter

c.1869C>A · VCV4292408

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,594,858)

Conditions

intellectual disability, autosomal recessive 42

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 21 of 27
REVEL	0.125	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.7	GERP -0.37, phastCons 1
Overall
CADD	36.0	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

No allele count reported in gnomAD v4.1 (AN 1,594,858). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: PGAP1
Protein: p.Cys623Ter
Coding: c.1869C>A
MANE Select: NM_024989
Type: single nucleotide variant
Location: chr2:196848030 (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.Cys623= Likely benign ★ same residue
PGAP1 p.Cys623fs Pathogenic ★ same residue
PGAP1 p.Gln466Ter Pathogenic ★★ same condition
PGAP1 p.Gln555Ter Pathogenic/Likely 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

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-cys623ter (accessed [today's date]).

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