Is PRPF31 p.Ser168= (c.504C>T) pathogenic?

PRPF31 p.Ser168= (c.504C>T) is classified Uncertain significance in PRPF31 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-13). Ultra-rare (popmax 0.0329%, mid); Associated with retinitis pigmentosa.

What condition is associated with PRPF31 p.Ser168= (c.504C>T)?

PRPF31 p.Ser168= (c.504C>T) is associated with retinitis pigmentosa (ClinVar).

How common is PRPF31 p.Ser168= (c.504C>T) in the general population?

PRPF31 p.Ser168= (c.504C>T) is ultra-rare (popmax 0.0329%, mid) (gnomAD).

How is Retinitis pigmentosa inherited?

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

PRPF31 p.Ser168=

c.504C>T · rs1281473715 · VCV892665

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0329%, mid)

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 -8.1	GERP -2.5
Overall
CADD	8.666	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0329% Middle Eastern · 2/6,084 alleles

Filtering AF 0.0058% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00241%

Overall 0.000558% 9/1,614,046 alleles · ultra-rare exomes 8/1,461,844 · genomes 1/152,202 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0329%	3,042
East Asian	0.00223%	44,902
European (non-Finnish)	0.000508%	196,669

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: PRPF31
Protein: p.Ser168=
Coding: c.504C>T
MANE Select: NM_015629
dbSNP: rs1281473715
Type: single nucleotide variant
Location: chr19:54123537 (GRCh38)
Gene constraint: LOEUF 0.347 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 77.69 · 30 PDB
Residue 168: an α-helix

Full PRPF31 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

PRPF31 c.1074-2A>G Pathogenic ★★ same condition
PRPF31 c.178-2A>G Pathogenic ★★ same condition
PRPF31 c.239-2A>G Pathogenic/Likely pathogenic ★★ same condition
PRPF31 c.322+1G>A Pathogenic/Likely pathogenic ★★ same condition
PRPF31 c.421-2A>G Pathogenic ★★ same condition
PRPF31 c.-9+1G>T Pathogenic/Likely pathogenic ★★ same condition
PRPF31 p.Arg354Ter Pathogenic/Likely pathogenic ★★ same condition
PRPF31 p.Cys191Ter 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/prpf31-p-ser168 (accessed [today's date]).

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