Is PRPF6 p.Pro19= (c.57G>A) pathogenic?

PRPF6 p.Pro19= (c.57G>A) is classified Conflicting classifications of pathogenicity in PRPF6 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2024-07-01). Rare (popmax 0.115%, mid); Associated with retinitis pigmentosa.

What condition is associated with PRPF6 p.Pro19= (c.57G>A)?

PRPF6 p.Pro19= (c.57G>A) is associated with retinitis pigmentosa (ClinVar).

How common is PRPF6 p.Pro19= (c.57G>A) in the general population?

PRPF6 p.Pro19= (c.57G>A) is rare (popmax 0.115%, mid) (gnomAD).

How is Retinitis pigmentosa inherited?

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

PRPF6 p.Pro19=

c.57G>A · rs779283679 · VCV339462

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

rare (popmax 0.115%, 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 -0.23	GERP -2.7, phastCons 0.059
Overall
CADD	10.34	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.115% Middle Eastern · 7/6,080 alleles

Filtering AF 0.054% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0383%

Overall 0.000561% 9/1,604,598 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.115%	869
Remaining individualsnot grpmax-eligible	0.00161%	62,036
European (non-Finnish)	8.5e-05%	1,175,930

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: PRPF6
Protein: p.Pro19=
Coding: c.57G>A
MANE Select: NM_012469
dbSNP: rs779283679
Type: single nucleotide variant
Location: chr20:63981302 (GRCh38)
Gene constraint: LOEUF 0.445 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 80.07 · 33 PDB
Residue 19: the 'disordered' region; a turn

Full PRPF6 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

PRPF6 p.Ala65Thr Uncertain significance ★★ ⚠ same condition
PRPF6 p.Arg703Trp Uncertain significance ★★ ⚠ same condition
PRPF6 p.His368Arg Uncertain significance ★★ ⚠ same condition
PRPF6 c.1186+13C>T Benign/Likely benign ★★ same condition
PRPF6 c.2340-11T>C Benign ★★ same condition
PRPF6 c.2431+15C>T Benign ★★ same condition
PRPF6 c.2546+15C>T Benign/Likely benign ★★ same condition
PRPF6 c.615+11A>G Benign/Likely 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/prpf6-p-pro19 (accessed [today's date]).

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