Is PRPF6 p.Ser403= (c.1209G>A) pathogenic?

PRPF6 p.Ser403= (c.1209G>A) is classified Benign in PRPF6 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-02-02). Common (popmax 12.6%, mid) — too common for a highly-penetrant pathogenic allele; Associated with retinitis pigmentosa.

What condition is associated with PRPF6 p.Ser403= (c.1209G>A)?

PRPF6 p.Ser403= (c.1209G>A) is associated with retinitis pigmentosa (ClinVar).

How is Retinitis pigmentosa inherited?

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

PRPF6 p.Ser403=

Q: How common is PRPF6 p.Ser403= (c.1209G>A) in the general population?

PRPF6 p.Ser403= (c.1209G>A) is common (popmax 12.6%, mid) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1209G>A · rs2427588 · VCV339472

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Common

common (popmax 12.6%, mid) — too common for a highly-penetrant pathogenic allele

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 -9	GERP -4
Overall
CADD	2.064	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 12.6% Middle Eastern · 765/6,058 alleles

Filtering AF 11.9% ClinGen BA1/BS1 input FAF95, joint · FAF99 11.6%

Overall 5.47% 88,353/1,613,890 alleles · common exomes 79,007/1,461,618 · genomes 9,346/152,272 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	12.6%	8
Amishnot grpmax-eligible	12%	8
Admixed American	6.42%	16
Ashkenazi Jewishnot grpmax-eligible	6.39%	16
African / African-American	6.09%	16
European (non-Finnish)	5.85%	17
Finnishnot grpmax-eligible	5.8%	17
Remaining individualsnot grpmax-eligible	5.62%	18
South Asian	0.974%	103
East Asian	0.0156%	6,413

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.Ser403=
Coding: c.1209G>A
MANE Select: NM_012469
dbSNP: rs2427588
Type: single nucleotide variant
Location: chr20:64010222 (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.Ser403Leu Uncertain significance ★★ ⚠ same residue
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

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-ser403 (accessed [today's date]).

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