Is PGAP2 p.Arg171Cys (c.511C>T) pathogenic?

PGAP2 p.Arg171Cys (c.511C>T) is classified Uncertain significance in PGAP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-26). AlphaMissense: likely benign (0.0958); Very rare (popmax 0.00329%, sas); Associated with Inborn genetic diseases.

What condition is associated with PGAP2 p.Arg171Cys (c.511C>T)?

PGAP2 p.Arg171Cys (c.511C>T) is associated with Inborn genetic diseases (ClinVar).

How common is PGAP2 p.Arg171Cys (c.511C>T) in the general population?

PGAP2 p.Arg171Cys (c.511C>T) is very rare (popmax 0.00329%, sas) (gnomAD).

What do computational predictors say about PGAP2 p.Arg171Cys (c.511C>T)?

AlphaMissense predicts likely benign (score 0.0958) — an in-silico prediction, not a clinical call.

PGAP2 p.Arg171Cys

c.511C>T · rs1313853886 · VCV3211648

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0958 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00329%, sas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0958	likely benign
REVEL	0.12	moderately benign-leaning
SaProt	LLR -10.89	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.2	GERP 1.8, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 14 kb · p 0.023 · regional, not allelic
Overall
CADD	23.9	PHRED · no single calibrated threshold — expert panels disagree

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM R110C vs ClinVar R171C) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00329% South Asian · 3/91,084 alleles

Filtering AF 0.000875% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000443%

Overall 0.000805% 13/1,614,180 alleles · very rare exomes 13/1,461,874 · genomes 0/152,306 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00329%	30,361
Remaining individualsnot grpmax-eligible	0.0016%	62,510
Finnishnot grpmax-eligible	0.00156%	64,032
African / African-American	0.00133%	75,042
European (non-Finnish)	0.000593%	168,575

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.Arg171Cys
Coding: c.511C>T
MANE Select: NM_014489
dbSNP: rs1313853886
Type: single nucleotide variant
Location: chr11:3824045 (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-arg171cys (accessed [today's date]).

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