Is PRPF8 p.Ala201= (c.603C>T) pathogenic?

PRPF8 p.Ala201= (c.603C>T) is classified Benign/Likely benign in PRPF8 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-07-27). Ultra-rare (popmax 0.0615%, sas); Associated with retinitis pigmentosa 13.

What condition is associated with PRPF8 p.Ala201= (c.603C>T)?

PRPF8 p.Ala201= (c.603C>T) is associated with retinitis pigmentosa 13 (ClinVar).

How common is PRPF8 p.Ala201= (c.603C>T) in the general population?

PRPF8 p.Ala201= (c.603C>T) is ultra-rare (popmax 0.0615%, 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.Ala201=

c.603C>T · rs148215037 · VCV1168313

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0615%, 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 0.15	GERP -5, phastCons 0.84
Overall
CADD	4.863	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0615% South Asian · 56/91,058 alleles

Filtering AF 0.0486% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.044%

Overall 0.0206% 332/1,613,872 alleles · ultra-rare exomes 308/1,461,892 · genomes 24/151,980 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.243%	411
South Asiangrpmax	0.0615%	1,626
Remaining individualsnot grpmax-eligible	0.0288%	3,473
Admixed American	0.0184%	5,449
European (non-Finnish)	0.0145%	6,901
African / African-American	0.004%	24,979
Finnishnot grpmax-eligible	0.00156%	63,986

Ashkenazi Jewish 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: PRPF8
Protein: p.Ala201=
Coding: c.603C>T
MANE Select: NM_006445
dbSNP: rs148215037
Type: single nucleotide variant
Location: chr17:1681870 (GRCh38)
Gene constraint: LOEUF 0.26 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 85.20 · 100 PDB
Residue 201: an α-helix

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.Ala201Thr Uncertain significance ★★ ⚠ same residue
PRPF8 p.Ala201Asp Uncertain significance ★ ⚠ same residue
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

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-ala201 (accessed [today's date]).

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