Is PPRC1 p.Arg366Gln (c.1097G>A) pathogenic?

PPRC1 p.Arg366Gln (c.1097G>A) is classified Uncertain significance in PPRC1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-10). AlphaMissense: likely benign (0.1212); Ultra-rare (popmax 0.0493%, mid).

How common is PPRC1 p.Arg366Gln (c.1097G>A) in the general population?

PPRC1 p.Arg366Gln (c.1097G>A) is ultra-rare (popmax 0.0493%, mid) (gnomAD).

What do computational predictors say about PPRC1 p.Arg366Gln (c.1097G>A)?

AlphaMissense predicts likely benign (score 0.1212) — an in-silico prediction, not a clinical call.

PPRC1 p.Arg366Gln

c.1097G>A · rs771195494 · VCV2211613

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1212 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0493%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1212	likely benign
REVEL	0.214	benign-leaning
SaProt	LLR -5.81	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 8.7	GERP 1.7, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 16 kb · p 0.94 · regional, not allelic
Overall
CADD	21.5	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 0.0493% Middle Eastern · 3/6,082 alleles

Filtering AF 0.0134% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00716%

Overall 0.00155% 25/1,613,770 alleles · ultra-rare exomes 24/1,461,540 · genomes 1/152,230 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0493%	2,027
African / African-American	0.00534%	18,736
South Asian	0.00329%	30,363
Remaining individualsnot grpmax-eligible	0.0032%	31,237
Admixed American	0.00167%	60,004
European (non-Finnish)	0.00102%	98,334

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: PPRC1
Protein: p.Arg366Gln
Coding: c.1097G>A
MANE Select: NM_015062
dbSNP: rs771195494
Type: single nucleotide variant
Location: chr10:102139605 (GRCh38)
Gene constraint: LOEUF 0.248 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 42.49

Full PPRC1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PPRC1 p.Arg366Gly Uncertain significance ★ same residue
PPRC1 p.Arg1428His Uncertain significance ★★ ⚠ same type
PPRC1 c.4551-5G>A Benign/Likely benign ★★ same type
PPRC1 p.Ala1005Val Uncertain significance ★ ⚠ same type
PPRC1 p.Ala1134Val Uncertain significance ★ ⚠ same type
PPRC1 p.Ala1192Val Uncertain significance ★ ⚠ same type
PPRC1 p.Ala1243Val Uncertain significance ★ ⚠ same type
PPRC1 p.Ala1258Thr Uncertain significance ★ ⚠ same type

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/pprc1-p-arg366gln (accessed [today's date]).

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