Is PRPF3 p.Ala673Val (c.2018C>T) pathogenic?

PRPF3 p.Ala673Val (c.2018C>T) is classified Uncertain significance in PRPF3 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-01-01). AlphaMissense: likely pathogenic (0.7263); Very rare (popmax 0.000169%, nfe); Associated with inherited retinal dystrophy.

What condition is associated with PRPF3 p.Ala673Val (c.2018C>T)?

PRPF3 p.Ala673Val (c.2018C>T) is associated with inherited retinal dystrophy (ClinVar).

How common is PRPF3 p.Ala673Val (c.2018C>T) in the general population?

PRPF3 p.Ala673Val (c.2018C>T) is very rare (popmax 0.000169%, nfe) (gnomAD).

What do computational predictors say about PRPF3 p.Ala673Val (c.2018C>T)?

AlphaMissense predicts likely pathogenic (score 0.7263) — an in-silico prediction, not a clinical call.

PRPF3 p.Ala673Val

c.2018C>T · VCV3249056

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7263 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000169%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

inherited retinal dystrophy

Computational evidence

Protein change
AlphaMissense	0.7263	likely pathogenic
REVEL	0.66	pathogenic-leaning
SaProt	LLR -6.33	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.9, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 6,516 bp · p 0.059 · regional, not allelic
Overall
CADD	28.5	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000169% European (non-Finnish) · 2/1,179,998 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000124% 2/1,614,096 alleles · very rare exomes 2/1,461,870 · genomes 0/152,226 · joint denominator

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.Ala673Val
Coding: c.2018C>T
MANE Select: NM_004698
Type: single nucleotide variant
Location: chr1:150352945 (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.Ala673= Benign/Likely benign ★★ 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-ala673val (accessed [today's date]).

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