Is PCARE p.Pro806= (c.2418C>T) pathogenic?

PCARE p.Pro806= (c.2418C>T) is classified Conflicting classifications of pathogenicity in PCARE (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2026-01-24). Rare (popmax 0.489%, afr); Associated with retinitis pigmentosa.

What condition is associated with PCARE p.Pro806= (c.2418C>T)?

PCARE p.Pro806= (c.2418C>T) is associated with retinitis pigmentosa (ClinVar).

How common is PCARE p.Pro806= (c.2418C>T) in the general population?

PCARE p.Pro806= (c.2418C>T) is rare (popmax 0.489%, afr) (gnomAD).

How is Retinitis pigmentosa inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

PCARE p.Pro806=

c.2418C>T · rs189042259 · VCV166761

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

rare (popmax 0.489%, afr)

Conditions

retinitis pigmentosa

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.4	GERP -3.6
Overall
CADD	0.704	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.489% African / African-American · 367/75,064 alleles

Filtering AF 0.448% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.431%

Overall 0.031% 501/1,614,252 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.489%	205
Middle Eastern	0.0825%	1,212
Admixed American	0.0483%	2,070
Remaining individualsnot grpmax-eligible	0.032%	3,125
European (non-Finnish)	0.00669%	14,937
South Asian	0.0011%	91,086

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: PCARE
Protein: p.Pro806=
Coding: c.2418C>T
MANE Select: NM_001029883
dbSNP: rs189042259
Type: single nucleotide variant
Location: chr2:29071844 (GRCh38)
Gene constraint: LOEUF 1.032 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 44.15 · 1 PDB

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

Disease context

retinitis pigmentosa — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Retinitis pigmentosa (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, Mitochondrial inheritance
Onset: Adolescent, Adult, Childhood
Prevalence: 1-5 / 10 000 (Europe)

Similar variants

PCARE p.Arg984Ter Pathogenic ★★ same condition
PCARE p.Gln1097Ter Pathogenic/Likely pathogenic ★★ same condition
PCARE p.Leu307Ter Pathogenic/Likely pathogenic ★★ same condition
PCARE p.Trp1001Ter Pathogenic/Likely pathogenic ★★ same condition
PCARE p.Trp720Ter Pathogenic/Likely pathogenic ★★ same condition
PCARE p.Trp941Ter Pathogenic/Likely pathogenic ★★ same condition
PCARE c.3669-5G>A Uncertain significance ★★ same condition
PCARE c.*1666C>T Uncertain significance ★★ same condition

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/pcare-p-pro806 (accessed [today's date]).

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