Is PCARE p.Ser484= (c.1452C>T) pathogenic?

PCARE p.Ser484= (c.1452C>T) is classified Benign in PCARE (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-02-03). Common (popmax 43.4%, eas) — too common for a highly-penetrant pathogenic allele; Associated with inherited retinal dystrophy.

What condition is associated with PCARE p.Ser484= (c.1452C>T)?

PCARE p.Ser484= (c.1452C>T) is associated with inherited retinal dystrophy, retinitis pigmentosa 54, retinitis pigmentosa (ClinVar).

PCARE p.Ser484=

Q: How common is PCARE p.Ser484= (c.1452C>T) in the general population?

PCARE p.Ser484= (c.1452C>T) is common (popmax 43.4%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1452C>T · rs13385188 · VCV335662

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Common

common (popmax 43.4%, eas) — 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 -1.7	GERP -3.3
Overall
CADD	0.867	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 43.4% East Asian · 19,464/44,846 alleles

Filtering AF 42.9% ClinGen BA1/BS1 input FAF95, joint · FAF99 42.7%

Overall 27.6% 444,616/1,613,810 alleles · common exomes 399,174/1,461,878 · genomes 45,442/151,932 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	43.4%	2
African / African-American	39.4%	3
Middle Eastern	33.7%	3
Remaining individualsnot grpmax-eligible	29.7%	3
Amishnot grpmax-eligible	28.7%	3
European (non-Finnish)	27.5%	4
Ashkenazi Jewishnot grpmax-eligible	26.9%	4
Admixed American	23.8%	4
South Asian	23.2%	4
Finnishnot grpmax-eligible	11.7%	9

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.Ser484=
Coding: c.1452C>T
MANE Select: NM_001029883
dbSNP: rs13385188
Type: single nucleotide variant
Location: chr2:29072810 (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 484: 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-ser484 (accessed [today's date]).

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