Is PRPF8 p.Pro2232= (c.6696C>T) pathogenic?

PRPF8 p.Pro2232= (c.6696C>T) is classified Likely benign in PRPF8 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-09-10). Very rare (popmax 0.00333%, amr).

How common is PRPF8 p.Pro2232= (c.6696C>T) in the general population?

PRPF8 p.Pro2232= (c.6696C>T) is very rare (popmax 0.00333%, amr) (gnomAD).

PRPF8 p.Pro2232=

c.6696C>T · rs760241443 · VCV1551232

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00333%, amr)

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 1.9	GERP -1.9, phastCons 1
Overall
CADD	9.165	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00333% Admixed American · 2/60,004 alleles

Filtering AF 0.000553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000207%

Overall 0.000496% 8/1,614,032 alleles · very rare exomes 5/1,461,840 · genomes 3/152,192 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.0101%	9,869
Admixed Americangrpmax	0.00333%	30,002
East Asian	0.00223%	44,898
European (non-Finnish)	0.000169%	590,019

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: PRPF8
Protein: p.Pro2232=
Coding: c.6696C>T
MANE Select: NM_006445
dbSNP: rs760241443
Type: single nucleotide variant
Location: chr17:1651265 (GRCh38)
Gene constraint: LOEUF 0.26 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 85.20 · 100 PDB
Residue 2232: the mpn domain; an α-helix

Full PRPF8 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PRPF8 p.Arg1935His Pathogenic/Likely pathogenic ★★ same type
PRPF8 p.Arg2310Gly Pathogenic/Likely pathogenic ★★ same type
PRPF8 p.Arg2310Lys Pathogenic ★★ ⚠ same type
PRPF8 p.Arg2310Ser Pathogenic ★★ ⚠ same type
PRPF8 p.Gln2321Ter Pathogenic/Likely pathogenic ★★ same type
PRPF8 p.His2309Arg Pathogenic ★★ ⚠ same type
PRPF8 p.His2309Pro Pathogenic/Likely pathogenic ★★ same type
PRPF8 p.His2313Pro Likely pathogenic ★★ ⚠ 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/prpf8-p-pro2232 (accessed [today's date]).

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