Is PCARE p.Arg86= (c.258G>A) pathogenic?

PCARE p.Arg86= (c.258G>A) is classified Benign in PCARE (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-02-03). Common (popmax 22.8%, nfe) — too common for a highly-penetrant pathogenic allele; Associated with inherited retinal dystrophy.

What condition is associated with PCARE p.Arg86= (c.258G>A)?

PCARE p.Arg86= (c.258G>A) is associated with inherited retinal dystrophy, retinitis pigmentosa 54, retinitis pigmentosa (ClinVar).

PCARE p.Arg86=

Q: How common is PCARE p.Arg86= (c.258G>A) in the general population?

PCARE p.Arg86= (c.258G>A) is common (popmax 22.8%, nfe) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.258G>A · rs62132765 · VCV335672

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Common

common (popmax 22.8%, nfe) — too common for a highly-penetrant pathogenic allele

Conditions

inherited retinal dystrophy

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 0.17	GERP -0.81
Overall
CADD	3.843	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 22.8% European (non-Finnish) · 269,564/1,179,972 alleles

Filtering AF 22.8% ClinGen BA1/BS1 input FAF95, joint · FAF99 22.7%

Overall 19.9% 321,375/1,614,078 alleles · common exomes 298,249/1,461,866 · genomes 23,126/152,212 · joint denominator

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	23.3%	4
European (non-Finnish)grpmax	22.8%	4
Middle Eastern	22.1%	5
Ashkenazi Jewishnot grpmax-eligible	20.4%	5
Remaining individualsnot grpmax-eligible	19.9%	5
Admixed American	12.9%	8
East Asian	11.5%	9
South Asian	10.9%	9
Finnishnot grpmax-eligible	9.3%	11
African / African-American	3.99%	25

Amish 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: PCARE
Protein: p.Arg86=
Coding: c.258G>A
MANE Select: NM_001029883
dbSNP: rs62132765
Type: single nucleotide variant
Location: chr2:29074004 (GRCh38)
Gene constraint: LOEUF 1.032 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 44.15 · 1 PDB
Residue 86: the 'disordered' region

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

Disease context

inherited retinal dystrophy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: retinitis pigmentosa 54 retinitis pigmentosa

Similar variants

PCARE c.3668+2T>C Likely pathogenic ★★ same condition
PCARE p.Arg1202Ter Pathogenic/Likely pathogenic ★★ same condition
PCARE p.Arg425Ter Pathogenic ★★ same condition
PCARE p.Arg613Ter Pathogenic ★★ same condition
PCARE p.Arg984Ter Pathogenic ★★ same condition
PCARE p.Gln1097Ter Pathogenic/Likely pathogenic ★★ same condition
PCARE p.Leu307Ter Pathogenic/Likely pathogenic ★★ same condition
PCARE p.Lys902Ter Pathogenic ★★ 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-arg86 (accessed [today's date]).

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