Is PCARE c.*1663C>T pathogenic?

PCARE c.1663C>T is classified Benign in PCARE (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-01-13). Common (popmax 84.7%, eas) — too common for a highly-penetrant pathogenic allele; Associated with retinitis pigmentosa.

What condition is associated with PCARE c.*1663C>T?

PCARE c.*1663C>T is associated with retinitis pigmentosa (ClinVar).

How is Retinitis pigmentosa inherited?

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

PCARE c.*1663C>T

Q: How common is PCARE c.*1663C>T in the general population?

PCARE c.*1663C>T is common (popmax 84.7%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

rs958584 · VCV335599

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 84.7%, eas) — too common for a highly-penetrant pathogenic allele

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 1.1	GERP -1.1, phastCons 0.064
Overall
CADD	6.665	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 84.7% East Asian · 4,374/5,162 alleles

Filtering AF 82.6% ClinGen BA1/BS1 input FAF95, joint · FAF99 81.8%

Overall 52.3% 79,599/152,200 alleles · common

Ancestry group	Frequency	1 in
East Asiangrpmax	84.7%	1
Amishnot grpmax-eligible	74.9%	1
Middle Eastern	58.8%	2
Ashkenazi Jewishnot grpmax-eligible	57.1%	2
Remaining individualsnot grpmax-eligible	55%	2
South Asian	51.9%	2
European (non-Finnish)	51.8%	2
African / African-American	50.2%	2
Admixed American	49.4%	2
Finnishnot grpmax-eligible	47.9%	2

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
Coding: c.*1663C>T
MANE Select: NM_001029883
dbSNP: rs958584
Type: single nucleotide variant
Location: chr2:29063206 (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-c-star-1663c-t (accessed [today's date]).

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