Is PPRC1 p.Pro940Arg (c.2819C>G) pathogenic?

PPRC1 p.Pro940Arg (c.2819C>G) is classified Uncertain significance in PPRC1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-10). AlphaMissense: likely benign (0.1739); Very rare (popmax 0.00223%, eas).

How common is PPRC1 p.Pro940Arg (c.2819C>G) in the general population?

PPRC1 p.Pro940Arg (c.2819C>G) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about PPRC1 p.Pro940Arg (c.2819C>G)?

AlphaMissense predicts likely benign (score 0.1739) — an in-silico prediction, not a clinical call.

PPRC1 p.Pro940Arg

c.2819C>G · VCV4143438

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1739 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1739	likely benign
REVEL	0.212	benign-leaning
SaProt	LLR -10.30	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 3.5	GERP 1.7, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 16 kb · p 0.94 · regional, not allelic
Overall
CADD	20.3	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 0.00223% East Asian · 1/44,886 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.00031% 5/1,613,974 alleles · very rare exomes 4/1,461,774 · genomes 1/152,200 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,886
Remaining individualsnot grpmax-eligible	0.0016%	62,478
African / African-American	0.00133%	74,928
European (non-Finnish)	0.000169%	589,984

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.Pro940Arg
Coding: c.2819C>G
MANE Select: NM_015062
Type: single nucleotide variant
Location: chr10:102141327 (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.Pro940Ala 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-pro940arg (accessed [today's date]).

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