Is PRCP p.Phe53Ile (c.157T>A) pathogenic?

PRCP p.Phe53Ile (c.157T>A) is classified Likely benign in PRCP (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-25). AlphaMissense: likely benign (0.1183); Very rare (popmax 0.000339%, nfe).

How common is PRCP p.Phe53Ile (c.157T>A) in the general population?

PRCP p.Phe53Ile (c.157T>A) is very rare (popmax 0.000339%, nfe) (gnomAD).

What do computational predictors say about PRCP p.Phe53Ile (c.157T>A)?

AlphaMissense predicts likely benign (score 0.1183) — an in-silico prediction, not a clinical call.

PRCP p.Phe53Ile

c.157T>A · VCV3424590

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1183 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000339%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1183	likely benign
REVEL	0.064	moderately benign-leaning
SaProt	LLR -8.33	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 0.41	GERP -1.5, phastCons 0.97
Regional constraint	o/e 1.03	unconstrained · MANE · 75 kb · p 0.51 · regional, not allelic
Overall
CADD	18.02	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 0.000339% European (non-Finnish) · 4/1,179,988 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.00031% 5/1,614,132 alleles · very rare exomes 5/1,461,810 · genomes 0/152,322 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0016%	62,500
European (non-Finnish)grpmax	0.000339%	294,997

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Phe53Ile
Coding: c.157T>A
MANE Select: NM_005040
Type: single nucleotide variant
Location: chr11:82900246 (GRCh38)
Gene constraint: LOEUF 1.119 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.99 · 1 PDB
Residue 53: a β-strand

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-phe53ile (accessed [today's date]).

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