Is PPCS p.Arg263Gln (c.788G>A) pathogenic?

PPCS p.Arg263Gln (c.788G>A) is classified Uncertain significance in PPCS (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-03-21). AlphaMissense: likely benign (0.1648); Very rare (popmax 0.00534%, afr); Associated with Inborn genetic diseases.

What condition is associated with PPCS p.Arg263Gln (c.788G>A)?

PPCS p.Arg263Gln (c.788G>A) is associated with Inborn genetic diseases (ClinVar).

How common is PPCS p.Arg263Gln (c.788G>A) in the general population?

PPCS p.Arg263Gln (c.788G>A) is very rare (popmax 0.00534%, afr) (gnomAD).

What do computational predictors say about PPCS p.Arg263Gln (c.788G>A)?

AlphaMissense predicts likely benign (score 0.1648) — an in-silico prediction, not a clinical call.

PPCS p.Arg263Gln

c.788G>A · rs368077055 · VCV1450466

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1648 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00534%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1648	likely benign
REVEL	0.231	benign-leaning
SaProt	LLR -11.19	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 1.6	GERP -4.6, phastCons 0.006
Regional constraint	o/e 0.69	unconstrained · MANE · 2,669 bp · p 5.9e-05 · regional, not allelic
Overall
CADD	19.61	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00534% African / African-American · 4/74,914 alleles

Filtering AF 0.00175% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.00031% 5/1,614,022 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00534%	18,728
European (non-Finnish)	8.47e-05%	1,180,013

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: PPCS
Protein: p.Arg263Gln
Coding: c.788G>A
MANE Select: NM_001395517 · reported on NM_024664
dbSNP: rs368077055
Type: single nucleotide variant
Location: chr1:42459778 (GRCh38)

Full PPCS 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

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/ppcs-p-arg263gln (accessed [today's date]).

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