Is PRPF6 p.Leu697= (c.2091G>C) pathogenic?

PRPF6 p.Leu697= (c.2091G>C) is classified Likely benign in PRPF6 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-31). Absent from gnomAD v4.1.

How common is PRPF6 p.Leu697= (c.2091G>C) in the general population?

PRPF6 p.Leu697= (c.2091G>C) is absent from gnomAD v4.1 (gnomAD).

PRPF6 p.Leu697=

c.2091G>C · rs2123098484 · VCV1104393

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

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 -0.44	GERP -0.42, phastCons 0.004
Overall
CADD	1.213	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.Leu697=
Coding: c.2091G>C
MANE Select: NM_012469
dbSNP: rs2123098484
Type: single nucleotide variant
Location: chr20:64027044 (GRCh38)
Gene constraint: LOEUF 0.445 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 80.07 · 33 PDB
Residue 697: an α-helix

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

Similar variants

PRPF6 p.Leu697Met 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
PRPF6 p.Ala65Thr 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-leu697 (accessed [today's date]).

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