Is PRPF6 p.Ser263= (c.789T>C) pathogenic?

PRPF6 p.Ser263= (c.789T>C) is classified Benign in PRPF6 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-10). Ultra-rare (popmax 0.0704%, sas).

How common is PRPF6 p.Ser263= (c.789T>C) in the general population?

PRPF6 p.Ser263= (c.789T>C) is ultra-rare (popmax 0.0704%, sas) (gnomAD).

PRPF6 p.Ser263=

c.789T>C · rs201442445 · VCV1573955

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0704%, sas)

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 -1.1	GERP 1, phastCons 0.004
Overall
CADD	9.094	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0704% South Asian · 64/90,970 alleles

Filtering AF 0.0565% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0515%

Overall 0.00459% 74/1,613,528 alleles · ultra-rare exomes 67/1,461,438 · genomes 7/152,090 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0704%	1,421
Remaining individualsnot grpmax-eligible	0.0144%	6,944
Admixed American	0.00167%	59,964

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.Ser263=
Coding: c.789T>C
MANE Select: NM_012469
dbSNP: rs201442445
Type: single nucleotide variant
Location: chr20:63999062 (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

Similar variants

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
PRPF6 p.Ala675Thr 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-ser263 (accessed [today's date]).

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