Is PRPF3 p.Arg641= (c.1923G>A) pathogenic?

PRPF3 p.Arg641= (c.1923G>A) is classified Benign in PRPF3 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-01-26). Common (popmax 7.24%, afr) — too common for a highly-penetrant pathogenic allele; Associated with retinitis pigmentosa.

What condition is associated with PRPF3 p.Arg641= (c.1923G>A)?

PRPF3 p.Arg641= (c.1923G>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.

PRPF3 p.Arg641=

Q: How common is PRPF3 p.Arg641= (c.1923G>A) in the general population?

PRPF3 p.Arg641= (c.1923G>A) is common (popmax 7.24%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1923G>A · rs79516325 · VCV292506

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Common

common (popmax 7.24%, afr) — 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 4	GERP 1.9, phastCons 1
Overall
CADD	11.7	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 7.24% African / African-American · 5,432/74,982 alleles

Filtering AF 7.08% ClinGen BA1/BS1 input FAF95, joint · FAF99 7.02%

Overall 0.374% 6,036/1,614,090 alleles · common exomes 2,966/1,461,868 · genomes 3,070/152,222 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	7.24%	14
Remaining individualsnot grpmax-eligible	0.48%	208
Admixed American	0.385%	260
Middle Eastern	0.132%	758
South Asian	0.0242%	4,140
European (non-Finnish)	0.00364%	27,442

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: PRPF3
Protein: p.Arg641=
Coding: c.1923G>A
MANE Select: NM_004698
dbSNP: rs79516325
Type: single nucleotide variant
Location: chr1:150352850 (GRCh38)
Gene constraint: LOEUF 0.087 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 73.75 · 30 PDB

Full PRPF3 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

PRPF3 p.Arg641Gln Uncertain significance ★★ ⚠ same residue
PRPF3 p.His499Pro Pathogenic ★★ same condition
PRPF3 p.Thr494Met Pathogenic ★★ same condition
PRPF3 p.Gln445Arg Uncertain significance ★★ same condition
PRPF3 p.Glu488Asp Uncertain significance ★★ ⚠ same condition
PRPF3 c.1760-12C>T Benign/Likely benign ★★ same condition
PRPF3 c.729-15C>T Benign/Likely benign ★★ same condition
PRPF3 c.*228A>G 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/prpf3-p-arg641 (accessed [today's date]).

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