Is PRPF31 p.Ser263= (c.789G>A) pathogenic?

PRPF31 p.Ser263= (c.789G>A) is classified Conflicting classifications of pathogenicity in PRPF31 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-05-04). Ultra-rare (popmax 0.0164%, mid); Associated with Inborn genetic diseases.

What condition is associated with PRPF31 p.Ser263= (c.789G>A)?

PRPF31 p.Ser263= (c.789G>A) is associated with Inborn genetic diseases (ClinVar).

How common is PRPF31 p.Ser263= (c.789G>A) in the general population?

PRPF31 p.Ser263= (c.789G>A) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

PRPF31 p.Ser263=

c.789G>A · rs760581700 · VCV1359721

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

Conditions

Inborn genetic diseases

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 -13	GERP -3.1
Overall
CADD	0.136	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0164% Middle Eastern · 1/6,084 alleles

Filtering AF 0.00106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00083%

Overall 0.00167% 27/1,613,356 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,084
African / African-American	0.004%	24,971
East Asian	0.00223%	44,876
South Asian	0.0022%	45,542
Admixed American	0.00167%	59,994
European (non-Finnish)	0.00161%	62,104

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: PRPF31
Protein: p.Ser263=
Coding: c.789G>A
MANE Select: NM_015629
dbSNP: rs760581700
Type: single nucleotide variant
Location: chr19:54124590 (GRCh38)
Gene constraint: LOEUF 0.347 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 77.69 · 30 PDB
Residue 263: the nop domain

Full PRPF31 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PRPF31 p.Ser263Leu Uncertain significance ★ ⚠ same residue
PRPF31 p.Ala235Gly Uncertain significance ★★ ⚠ same condition
PRPF31 p.Ala254Thr Uncertain significance ★★ same condition
PRPF31 p.Arg357Cys Uncertain significance ★★ ⚠ same condition
PRPF31 p.Arg372Gln Uncertain significance ★★ ⚠ same condition
PRPF31 p.Arg442His Uncertain significance ★★ ⚠ same condition
PRPF31 p.Asn218Asp Uncertain significance ★★ ⚠ same condition
PRPF31 p.Asn240His Uncertain significance ★★ ⚠ 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/prpf31-p-ser263 (accessed [today's date]).

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