Is PRPF3 p.Ala673= (c.2019G>A) pathogenic?

PRPF3 p.Ala673= (c.2019G>A) is classified Benign/Likely benign in PRPF3 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-10-21). Rare (popmax 0.437%, eas); Associated with inherited retinal dystrophy.

What condition is associated with PRPF3 p.Ala673= (c.2019G>A)?

PRPF3 p.Ala673= (c.2019G>A) is associated with inherited retinal dystrophy (ClinVar).

How common is PRPF3 p.Ala673= (c.2019G>A) in the general population?

PRPF3 p.Ala673= (c.2019G>A) is rare (popmax 0.437%, eas) (gnomAD).

PRPF3 p.Ala673=

c.2019G>A · rs189302002 · VCV1915117

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.437%, eas)

Conditions

inherited retinal dystrophy

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 -0.82	GERP -3.7
Overall
CADD	6.61	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.437% East Asian · 196/44,870 alleles

Filtering AF 0.387% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.367%

Overall 0.0152% 245/1,614,100 alleles · rare exomes 236/1,461,874 · genomes 9/152,226 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.437%	229
African / African-American	0.008%	12,505
Remaining individualsnot grpmax-eligible	0.0064%	15,627
Admixed American	0.00333%	30,002
European (non-Finnish)	0.00314%	31,892

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.Ala673=
Coding: c.2019G>A
MANE Select: NM_004698
dbSNP: rs189302002
Type: single nucleotide variant
Location: chr1:150352946 (GRCh38)
Gene constraint: LOEUF 0.087 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 73.75 · 30 PDB
Residue 673: an α-helix

Full PRPF3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

inherited retinal dystrophy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PRPF3 p.Ala673Val Uncertain significance ★ ⚠ same residue
PRPF3 p.Ala673Gly Uncertain significance ★ ⚠ same residue
PRPF3 p.Pro493Ser Pathogenic ★★ same condition
PRPF3 p.Thr494Met Pathogenic ★★ same condition
PRPF3 p.Gln461Glu Uncertain significance ★★ ⚠ same condition
PRPF3 p.Ile560Met Uncertain significance ★★ ⚠ same condition
PRPF3 p.Lys662Arg Uncertain significance ★★ ⚠ same condition
PRPF3 p.Leu235= 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/prpf3-p-ala673 (accessed [today's date]).

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