Is PGAP1 p.Arg803Cys (c.2407C>T) pathogenic?

PGAP1 p.Arg803Cys (c.2407C>T) is classified Uncertain significance in PGAP1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-06-12). AlphaMissense: likely benign (0.072); Ultra-rare (popmax 0.02%, afr); Associated with intellectual disability, autosomal recessive 42.

What condition is associated with PGAP1 p.Arg803Cys (c.2407C>T)?

PGAP1 p.Arg803Cys (c.2407C>T) is associated with intellectual disability, autosomal recessive 42 (ClinVar).

How common is PGAP1 p.Arg803Cys (c.2407C>T) in the general population?

PGAP1 p.Arg803Cys (c.2407C>T) is ultra-rare (popmax 0.02%, afr) (gnomAD).

What do computational predictors say about PGAP1 p.Arg803Cys (c.2407C>T)?

AlphaMissense predicts likely benign (score 0.072) — an in-silico prediction, not a clinical call.

PGAP1 p.Arg803Cys

c.2407C>T · rs556240126 · VCV2456338

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.072 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.02%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

intellectual disability, autosomal recessive 42

Computational evidence

Protein change
AlphaMissense	0.072	likely benign
REVEL	0.11	moderately benign-leaning
SaProt	LLR -7.68	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.73	GERP -0.85
Regional constraint	o/e 0.92	unconstrained · MANE · 85 kb · p 0.0064 · regional, not allelic
Overall
CADD	16.39	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.02% African / African-American · 15/74,966 alleles

Filtering AF 0.0123% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00988%

Overall 0.00243% 39/1,608,078 alleles · ultra-rare exomes 25/1,455,816 · genomes 14/152,262 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.02%	4,998
South Asian	0.0111%	9,038
Remaining individualsnot grpmax-eligible	0.00644%	15,529
Admixed American	0.00502%	19,926
European (non-Finnish)	0.000595%	167,980

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.Arg803Cys
Coding: c.2407C>T
MANE Select: NM_024989
dbSNP: rs556240126
Type: single nucleotide variant
Location: chr2:196844006 (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.Arg803His Uncertain significance ★★ ⚠ 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
PGAP1 p.Arg250His 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-arg803cys (accessed [today's date]).

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