Is PRPF6 p.Val267= (c.801C>T) pathogenic?

PRPF6 p.Val267= (c.801C>T) is classified Likely benign in PRPF6 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-01-07). Rare (popmax 0.167%, afr); Associated with retinitis pigmentosa.

What condition is associated with PRPF6 p.Val267= (c.801C>T)?

PRPF6 p.Val267= (c.801C>T) is associated with retinitis pigmentosa (ClinVar).

How common is PRPF6 p.Val267= (c.801C>T) in the general population?

PRPF6 p.Val267= (c.801C>T) is rare (popmax 0.167%, afr) (gnomAD).

How is Retinitis pigmentosa inherited?

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

PRPF6 p.Val267=

c.801C>T · rs138336365 · VCV724373

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

rare (popmax 0.167%, afr)

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 -0.64	GERP -4, phastCons 0.004
Overall
CADD	5.257	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.167% African / African-American · 125/75,018 alleles

Filtering AF 0.143% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.134%

Overall 0.0419% 676/1,613,804 alleles · rare exomes 578/1,461,574 · genomes 98/152,230 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.167%	600
Remaining individualsnot grpmax-eligible	0.0768%	1,302
European (non-Finnish)	0.039%	2,565
Admixed American	0.0267%	3,749
South Asian	0.0264%	3,792
East Asian	0.00669%	14,955

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.Val267=
Coding: c.801C>T
MANE Select: NM_012469
dbSNP: rs138336365
Type: single nucleotide variant
Location: chr20:63999074 (GRCh38)
Gene constraint: LOEUF 0.445 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 80.07 · 33 PDB

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-val267 (accessed [today's date]).

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