Is PRPF8 p.Pro949= (c.2847G>A) pathogenic?

PRPF8 p.Pro949= (c.2847G>A) is classified Benign in PRPF8 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-02-03). Common (popmax 52.9%, afr) — too common for a highly-penetrant pathogenic allele; Associated with retinitis pigmentosa.

What condition is associated with PRPF8 p.Pro949= (c.2847G>A)?

PRPF8 p.Pro949= (c.2847G>A) is associated with retinitis pigmentosa, inherited retinal dystrophy (ClinVar).

How is Retinitis pigmentosa inherited?

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

PRPF8 p.Pro949=

Q: How common is PRPF8 p.Pro949= (c.2847G>A) in the general population?

PRPF8 p.Pro949= (c.2847G>A) is common (popmax 52.9%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.2847G>A · rs33965342 · VCV321898

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Common

common (popmax 52.9%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

retinitis pigmentosa

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 -0.3	GERP -4, phastCons 0.009
Overall
CADD	9.503	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 52.9% African / African-American · 39,637/74,896 alleles

Filtering AF 52.5% ClinGen BA1/BS1 input FAF95, joint · FAF99 52.3%

Overall 21.4% 344,938/1,613,812 alleles · common exomes 301,526/1,461,854 · genomes 43,412/151,958 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	52.9%	2
Ashkenazi Jewishnot grpmax-eligible	30%	3
Middle Eastern	23.2%	4
Remaining individualsnot grpmax-eligible	22.4%	4
European (non-Finnish)	20.6%	5
Finnishnot grpmax-eligible	19.1%	5
South Asian	16.8%	6
Admixed American	13.1%	8
Amishnot grpmax-eligible	6.8%	15
East Asian	5.23%	19

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.Pro949=
Coding: c.2847G>A
MANE Select: NM_006445
dbSNP: rs33965342
Type: single nucleotide variant
Location: chr17:1675645 (GRCh38)
Gene constraint: LOEUF 0.26 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 85.20 · 100 PDB
Residue 949: an α-helix; 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

Also linked: inherited retinal dystrophy

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.Gln2321Ter Pathogenic/Likely pathogenic ★★ same condition
PRPF8 p.His2313Pro Likely pathogenic ★★ ⚠ same condition
PRPF8 p.Pro2301Ser Pathogenic/Likely pathogenic ★★ ⚠ same condition
PRPF8 p.Thr1931Met Pathogenic/Likely pathogenic ★★ ⚠ same condition
PRPF8 c.1719+4A>G Uncertain significance ★★ same condition
PRPF8 p.Ala1704Thr 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-pro949 (accessed [today's date]).

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