Is PRCP p.Val217Ile (c.649G>A) pathogenic?

PRCP p.Val217Ile (c.649G>A) is classified Uncertain significance in PRCP (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-26). AlphaMissense: likely benign (0.072); Very rare (popmax 8.71e-05%, nfe).

How common is PRCP p.Val217Ile (c.649G>A) in the general population?

PRCP p.Val217Ile (c.649G>A) is very rare (popmax 8.71e-05%, nfe) (gnomAD).

What do computational predictors say about PRCP p.Val217Ile (c.649G>A)?

AlphaMissense predicts likely benign (score 0.072) — an in-silico prediction, not a clinical call.

PRCP p.Val217Ile

c.649G>A · VCV3424587

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.072 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.71e-05%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.072	likely benign
REVEL	0.221	benign-leaning
SaProt	LLR -6.68	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.9	GERP -3.3
Regional constraint	o/e 1.03	unconstrained · MANE · 75 kb · p 0.51 · regional, not allelic
Overall
CADD	8.37	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 8.71e-05% European (non-Finnish) · 1/1,147,990 alleles

Overall 6.44e-05% 1/1,552,928 alleles · very rare exomes 1/1,400,896 · genomes 0/152,032 · joint denominator

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: PRCP
Protein: p.Val217Ile
Coding: c.649G>A
MANE Select: NM_005040
Type: single nucleotide variant
Location: chr11:82850016 (GRCh38)
Gene constraint: LOEUF 1.119 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.99 · 1 PDB
Residue 217: the 'sks domain' region; an α-helix

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

Similar variants

PRCP p.Ala201Glu Uncertain significance ★ ⚠ same type
PRCP p.Ala260Gly Uncertain significance ★ ⚠ same type
PRCP p.Arg163Lys Uncertain significance ★ ⚠ same type
PRCP p.Arg227Ser Uncertain significance ★ ⚠ same type
PRCP p.Arg239Ser Uncertain significance ★ ⚠ same type
PRCP p.Arg460Cys Uncertain significance ★ same type
PRCP p.Arg460His Uncertain significance ★ same type
PRCP p.Arg71Gln 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/prcp-p-val217ile (accessed [today's date]).

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