Is PRPF8 p.Phe230= (c.690C>T) pathogenic?

PRPF8 p.Phe230= (c.690C>T) is classified Benign/Likely benign in PRPF8 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-12-14). Rare (popmax 0.429%, sas); Associated with retinitis pigmentosa 13.

What condition is associated with PRPF8 p.Phe230= (c.690C>T)?

PRPF8 p.Phe230= (c.690C>T) is associated with retinitis pigmentosa 13 (ClinVar).

How common is PRPF8 p.Phe230= (c.690C>T) in the general population?

PRPF8 p.Phe230= (c.690C>T) is rare (popmax 0.429%, sas) (gnomAD).

How is Retinitis pigmentosa inherited?

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

PRPF8 p.Phe230=

c.690C>T · rs200640834 · VCV810992

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.429%, sas)

Conditions

retinitis pigmentosa 13

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 2.2	GERP 0.5, phastCons 1
Overall
CADD	6.497	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.429% South Asian · 391/91,090 alleles

Filtering AF 0.394% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.38%

Overall 0.0258% 416/1,614,120 alleles · rare exomes 392/1,461,888 · genomes 24/152,232 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.429%	233
Remaining individualsnot grpmax-eligible	0.0336%	2,977
Middle Eastern	0.0165%	6,062
African / African-American	0.00267%	37,501
European (non-Finnish)	8.47e-05%	1,180,016

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: PRPF8
Protein: p.Phe230=
Coding: c.690C>T
MANE Select: NM_006445
dbSNP: rs200640834
Type: single nucleotide variant
Location: chr17:1681654 (GRCh38)
Gene constraint: LOEUF 0.26 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 85.20 · 100 PDB

Full PRPF8 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

retinitis pigmentosa 13 — 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

PRPF8 p.Arg1935His Pathogenic/Likely pathogenic ★★ same condition
PRPF8 p.Arg2310Gly Pathogenic/Likely pathogenic ★★ same condition
PRPF8 p.Arg2310Lys Pathogenic ★★ ⚠ same condition
PRPF8 p.His2309Arg Pathogenic ★★ ⚠ same condition
PRPF8 p.His2309Pro Pathogenic/Likely pathogenic ★★ same condition
PRPF8 p.Thr1931Met Pathogenic/Likely pathogenic ★★ ⚠ same condition
PRPF8 p.Tyr2326Ter Pathogenic/Likely pathogenic ★★ same condition
PRPF8 c.1719+4A>G 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/prpf8-p-phe230 (accessed [today's date]).

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