Is PRPF6 p.Arg866= (c.2598C>T) pathogenic?

PRPF6 p.Arg866= (c.2598C>T) is classified Likely benign in PRPF6 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-01-28). Absent from gnomAD v4.1.

How common is PRPF6 p.Arg866= (c.2598C>T) in the general population?

PRPF6 p.Arg866= (c.2598C>T) is absent from gnomAD v4.1 (gnomAD).

PRPF6 p.Arg866=

c.2598C>T · rs919476598 · VCV1658963

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Absent

absent from gnomAD v4.1

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 -0.38, phastCons 0.22
Overall
CADD	8.391	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: PRPF6
Protein: p.Arg866=
Coding: c.2598C>T
MANE Select: NM_012469
dbSNP: rs919476598
Type: single nucleotide variant
Location: chr20:64031969 (GRCh38)
Gene constraint: LOEUF 0.445 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 80.07 · 33 PDB
Residue 866: an α-helix

Full PRPF6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PRPF6 p.Arg866Cys Uncertain significance ★ ⚠ same residue
PRPF6 p.Arg866His Uncertain significance ★ ⚠ same residue
PRPF6 c.2028+5G>A Uncertain significance ★★ same type
PRPF6 c.2205+5G>A Uncertain significance ★★ same type
PRPF6 c.439-19G>A Uncertain significance ★★ same type
PRPF6 p.Ala246Val Uncertain significance ★★ ⚠ same type
PRPF6 p.Ala380Thr Uncertain significance ★★ ⚠ same type
PRPF6 p.Ala564Thr Uncertain significance ★★ ⚠ same type

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-arg866 (accessed [today's date]).

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