Is PGAP2 p.Arg264Trp (c.790C>T) pathogenic?

PGAP2 p.Arg264Trp (c.790C>T) is classified Uncertain significance in PGAP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-15). AlphaMissense: ambiguous (0.4479); Ultra-rare (popmax 0.014%, nfe); Associated with Inborn genetic diseases.

What condition is associated with PGAP2 p.Arg264Trp (c.790C>T)?

PGAP2 p.Arg264Trp (c.790C>T) is associated with Inborn genetic diseases (ClinVar).

How common is PGAP2 p.Arg264Trp (c.790C>T) in the general population?

PGAP2 p.Arg264Trp (c.790C>T) is ultra-rare (popmax 0.014%, nfe) (gnomAD).

What do computational predictors say about PGAP2 p.Arg264Trp (c.790C>T)?

AlphaMissense predicts ambiguous (score 0.4479) — an in-silico prediction, not a clinical call.

PGAP2 p.Arg264Trp

c.790C>T · VCV3305934

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4479 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.014%, nfe)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.4479	ambiguous
REVEL	0.201	benign-leaning
SaProt	LLR -10.32	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.9	GERP 1.9, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 14 kb · p 0.023 · regional, not allelic
Overall
CADD	24.8	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 R203W vs ClinVar R264W) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.014% European (non-Finnish) · 165/1,180,034 alleles

Filtering AF 0.0122% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0116%

Overall 0.0108% 174/1,614,066 alleles · ultra-rare exomes 163/1,461,872 · genomes 11/152,194 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.014%	7,152
Admixed American	0.005%	20,001
African / African-American	0.004%	24,977
Finnishnot grpmax-eligible	0.00312%	32,016
East Asian	0.00223%	44,890

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.Arg264Trp
Coding: c.790C>T
MANE Select: NM_014489
Type: single nucleotide variant
Location: chr11:3825101 (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

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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-arg264trp (accessed [today's date]).

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