Is PGAP2 p.Arg79Cys (c.235C>T) pathogenic?

PGAP2 p.Arg79Cys (c.235C>T) is classified Uncertain significance in PGAP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-16). Very rare (popmax 0.00769%, sas); Associated with Inborn genetic diseases.

What condition is associated with PGAP2 p.Arg79Cys (c.235C>T)?

PGAP2 p.Arg79Cys (c.235C>T) is associated with Inborn genetic diseases (ClinVar).

How common is PGAP2 p.Arg79Cys (c.235C>T) in the general population?

PGAP2 p.Arg79Cys (c.235C>T) is very rare (popmax 0.00769%, sas) (gnomAD).

PGAP2 p.Arg79Cys

c.235C>T · rs138755774 · VCV3211646

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00769%, sas)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.138	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Pangolin	Δ0.38	gain · loss 0.00 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP 3.4	GERP 1.9, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 14 kb · p 0.023 · regional, not allelic
Overall
CADD	29.1	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00769% South Asian · 7/91,080 alleles

Filtering AF 0.00359% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00255%

Overall 0.00186% 30/1,614,126 alleles · very rare exomes 23/1,461,854 · genomes 7/152,272 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0144%	6,945
South Asiangrpmax	0.00769%	13,011
African / African-American	0.00533%	18,762
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,606
Admixed American	0.00167%	60,002
European (non-Finnish)	0.000678%	147,501

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: PGAP2
Protein: p.Arg79Cys
Coding: c.235C>T
MANE Select: NM_014489
dbSNP: rs138755774
Type: single nucleotide variant
Location: chr11:3817422 (GRCh38)
Gene constraint: LOEUF 0.871 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.00

Full PGAP2 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

Similar variants

PGAP2 p.Ala187Thr Uncertain significance ★★ ⚠ same condition
PGAP2 p.Ala33Thr Uncertain significance ★★ ⚠ same condition
PGAP2 p.Arg238Cys Uncertain significance ★★ ⚠ same condition
PGAP2 p.Glu204Lys Uncertain significance ★★ ⚠ same condition
PGAP2 p.Leu161Phe Uncertain significance ★★ ⚠ same condition
PGAP2 p.Val183Met Uncertain significance ★★ ⚠ same condition
PGAP2 p.Val4Ile Uncertain significance ★★ ⚠ same condition
PGAP2 p.Val182Ile Benign/Likely benign ★★ 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/pgap2-p-arg79cys (accessed [today's date]).

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