Is PRCP p.Phe209Ser (c.626T>C) pathogenic?

PRCP p.Phe209Ser (c.626T>C) is classified Uncertain significance in PRCP (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-03). AlphaMissense: likely pathogenic (0.6096); No allele count reported in gnomAD v4.1 (AN 1,459,312).

How common is PRCP p.Phe209Ser (c.626T>C) in the general population?

PRCP p.Phe209Ser (c.626T>C) is no allele count reported in gnomAD v4.1 (AN 1,459,312) (gnomAD).

What do computational predictors say about PRCP p.Phe209Ser (c.626T>C)?

AlphaMissense predicts likely pathogenic (score 0.6096) — an in-silico prediction, not a clinical call.

PRCP p.Phe209Ser

c.626T>C · rs2495652841 · VCV2543038

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6096 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,459,312)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6096	likely pathogenic
REVEL	0.915	moderately pathogenic-leaning
SaProt	LLR -11.78	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.6, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 75 kb · p 0.51 · regional, not allelic
Overall
CADD	29.7	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

No allele count reported in gnomAD v4.1 (AN 1,459,312). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: PRCP
Protein: p.Phe209Ser
Coding: c.626T>C
MANE Select: NM_005040
dbSNP: rs2495652841
Type: single nucleotide variant
Location: chr11:82850039 (GRCh38)
Gene constraint: LOEUF 1.119 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.99 · 1 PDB
Residue 209: the 'sks domain' region

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-phe209ser (accessed [today's date]).

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