Is PRPF6 p.Pro14= (c.42C>T) pathogenic?

PRPF6 p.Pro14= (c.42C>T) is classified Benign in PRPF6 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-26). Low-frequency (popmax 1.88%, eas); Associated with inherited retinal dystrophy.

What condition is associated with PRPF6 p.Pro14= (c.42C>T)?

PRPF6 p.Pro14= (c.42C>T) is associated with inherited retinal dystrophy, retinitis pigmentosa (ClinVar).

How common is PRPF6 p.Pro14= (c.42C>T) in the general population?

PRPF6 p.Pro14= (c.42C>T) is low-frequency (popmax 1.88%, eas) (gnomAD).

PRPF6 p.Pro14=

c.42C>T · rs186249212 · VCV339461

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.88%, eas)

Conditions

inherited retinal dystrophy

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 -0.79	GERP -2.8, phastCons 0.001
Overall
CADD	6.874	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.88% East Asian · 839/44,626 alleles

Filtering AF 1.77% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.73%

Overall 0.0574% 922/1,607,534 alleles · low-frequency

Ancestry group	Frequency	1 in
East Asiangrpmax	1.88%	53
Remaining individualsnot grpmax-eligible	0.121%	829
South Asian	0.00444%	22,520
Admixed American	0.00169%	59,322
European (non-Finnish)	0.000255%	392,392

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.Pro14=
Coding: c.42C>T
MANE Select: NM_012469
dbSNP: rs186249212
Type: single nucleotide variant
Location: chr20:63981287 (GRCh38)
Gene constraint: LOEUF 0.445 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 80.07 · 33 PDB
Residue 14: the 'disordered' region; an α-helix

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

Disease context

inherited retinal dystrophy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: retinitis pigmentosa

Similar variants

PRPF6 p.Ala65Thr Uncertain significance ★★ ⚠ same condition
PRPF6 p.Arg703Trp Uncertain significance ★★ ⚠ same condition
PRPF6 p.His368Arg Uncertain significance ★★ ⚠ same condition
PRPF6 p.Ile919Val Uncertain significance ★★ ⚠ same condition
PRPF6 p.Pro282Leu Uncertain significance ★★ ⚠ same condition
PRPF6 p.Val411Ile Uncertain significance ★★ ⚠ same condition
PRPF6 c.1186+13C>T Benign/Likely benign ★★ same condition
PRPF6 c.2340-11T>C 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-pro14 (accessed [today's date]).

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