Is PGAP2 p.Arg16Gln (c.47G>A) pathogenic?

PGAP2 p.Arg16Gln (c.47G>A) is classified Uncertain significance in PGAP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-06). AlphaMissense: likely benign (0.1653); Ultra-rare (popmax 0.0187%, afr); Associated with Inborn genetic diseases.

What condition is associated with PGAP2 p.Arg16Gln (c.47G>A)?

PGAP2 p.Arg16Gln (c.47G>A) is associated with Inborn genetic diseases (ClinVar).

How common is PGAP2 p.Arg16Gln (c.47G>A) in the general population?

PGAP2 p.Arg16Gln (c.47G>A) is ultra-rare (popmax 0.0187%, afr) (gnomAD).

What do computational predictors say about PGAP2 p.Arg16Gln (c.47G>A)?

AlphaMissense predicts likely benign (score 0.1653) — an in-silico prediction, not a clinical call.

PGAP2 p.Arg16Gln

c.47G>A · rs144780584 · VCV2459988

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1653 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0187%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1653	likely benign
REVEL	0.265	benign-leaning
SaProt	LLR -9.04	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 12	GERP 1.9, phastCons 1
Regional constraint	o/e 0.48	unconstrained · MANE · 161 bp · p 1.5e-05 · regional, not allelic
Overall
CADD	29.7	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 0.0187% African / African-American · 14/74,908 alleles

Filtering AF 0.0112% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00905%

Overall 0.00161% 26/1,613,968 alleles · ultra-rare exomes 15/1,461,798 · genomes 11/152,170 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0187%	5,351
Finnishnot grpmax-eligible	0.00156%	64,032
South Asian	0.0011%	91,090
European (non-Finnish)	0.000847%	117,997

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.Arg16Gln
Coding: c.47G>A
MANE Select: NM_014489
dbSNP: rs144780584
Type: single nucleotide variant
Location: chr11:3811306 (GRCh38)
Gene constraint: LOEUF 0.871 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.00
Residue 16: a UniProt-annotated variant site (in hpmrs3)

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.Arg16Trp Pathogenic same residue
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

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-arg16gln (accessed [today's date]).

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