Is PRPF8 p.Ser1027= (c.3081A>T) pathogenic?

PRPF8 p.Ser1027= (c.3081A>T) is classified Conflicting classifications of pathogenicity in PRPF8 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-09-14). Ultra-rare (popmax 0.0103%, nfe); Associated with retinitis pigmentosa.

What condition is associated with PRPF8 p.Ser1027= (c.3081A>T)?

PRPF8 p.Ser1027= (c.3081A>T) is associated with retinitis pigmentosa (ClinVar).

How common is PRPF8 p.Ser1027= (c.3081A>T) in the general population?

PRPF8 p.Ser1027= (c.3081A>T) is ultra-rare (popmax 0.0103%, nfe) (gnomAD).

How is Retinitis pigmentosa inherited?

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

PRPF8 p.Ser1027=

c.3081A>T · rs201573889 · VCV891301

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0103%, nfe)

Conditions

retinitis pigmentosa

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -3.8	GERP -5.5
Overall
CADD	1.103	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0103% European (non-Finnish) · 121/1,179,472 alleles

Filtering AF 0.00876% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0082%

Overall 0.00775% 125/1,613,358 alleles · ultra-rare exomes 119/1,461,138 · genomes 6/152,220 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0103%	9,748
Remaining individualsnot grpmax-eligible	0.0048%	20,824
Finnishnot grpmax-eligible	0.00157%	63,896

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.Ser1027=
Coding: c.3081A>T
MANE Select: NM_006445
dbSNP: rs201573889
Type: single nucleotide variant
Location: chr17:1674660 (GRCh38)
Gene constraint: LOEUF 0.26 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 85.20 · 100 PDB
Residue 1027: a β-strand; the 'reverse transcriptase homology domain' region

Full PRPF8 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

PRPF8 p.Arg1935His Pathogenic/Likely pathogenic ★★ same condition
PRPF8 p.Arg2310Gly Pathogenic/Likely pathogenic ★★ same condition
PRPF8 c.1719+4A>G Uncertain significance ★★ same condition
PRPF8 p.Arg309His Uncertain significance ★★ ⚠ same condition
PRPF8 p.Asp1598Asn Uncertain significance ★★ ⚠ same condition
PRPF8 p.Thr1102Lys Uncertain significance ★★ same condition
PRPF8 p.Thr2195Ser Uncertain significance ★★ ⚠ same condition
PRPF8 c.101-3C>T Benign ★★ 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-ser1027 (accessed [today's date]).

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