Is PRCC p.Pro333Arg (c.998C>G) pathogenic?

PRCC p.Pro333Arg (c.998C>G) is classified Uncertain significance in PRCC (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-22). AlphaMissense: likely benign (0.1915); Very rare (popmax 0.00667%, amr).

How common is PRCC p.Pro333Arg (c.998C>G) in the general population?

PRCC p.Pro333Arg (c.998C>G) is very rare (popmax 0.00667%, amr) (gnomAD).

What do computational predictors say about PRCC p.Pro333Arg (c.998C>G)?

AlphaMissense predicts likely benign (score 0.1915) — an in-silico prediction, not a clinical call.

PRCC p.Pro333Arg

c.998C>G · rs768338970 · VCV3218308

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1915 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00667%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1915	likely benign
REVEL	0.055	moderately benign-leaning
SaProt	LLR -9.26	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 6	GERP 2.1, phastCons 1
Regional constraint	o/e 1.08	unconstrained · MANE · 4,824 bp · p 0.34 · regional, not allelic
Overall
CADD	24.8	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 0.00667% Admixed American · 4/60,004 alleles

Filtering AF 0.00226% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00135%

Overall 0.0013% 21/1,614,022 alleles · very rare exomes 14/1,461,836 · genomes 7/152,186 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00667%	15,001
African / African-American	0.004%	24,974
Remaining individualsnot grpmax-eligible	0.0032%	31,244
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: PRCC
Protein: p.Pro333Arg
Coding: c.998C>G
MANE Select: NM_005973
dbSNP: rs768338970
Type: single nucleotide variant
Location: chr1:156787089 (GRCh38)
Gene constraint: LOEUF 0.403 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 59.89

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

Similar variants

PRCC p.Asp341Gly Uncertain significance ★★ ⚠ same type
PRCC p.Ala283Thr Uncertain significance ★ ⚠ same type
PRCC p.Ala356Thr Uncertain significance ★ ⚠ same type
PRCC p.Arg219Thr Uncertain significance ★ ⚠ same type
PRCC p.Arg467Gln Uncertain significance ★ ⚠ same type
PRCC p.Arg482Cys Uncertain significance ★ ⚠ same type
PRCC p.Asn189Ser Uncertain significance ★ ⚠ same type
PRCC p.Asp214His 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/prcc-p-pro333arg (accessed [today's date]).

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