Is PRPF31 p.Val489= (c.1467C>T) pathogenic?

PRPF31 p.Val489= (c.1467C>T) is classified Benign in PRPF31 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-02-03). Common (popmax 10.2%, sas) — too common for a highly-penetrant pathogenic allele; Associated with inherited retinal dystrophy.

What condition is associated with PRPF31 p.Val489= (c.1467C>T)?

PRPF31 p.Val489= (c.1467C>T) is associated with inherited retinal dystrophy, retinitis pigmentosa 11, retinitis pigmentosa (ClinVar).

PRPF31 p.Val489=

Q: How common is PRPF31 p.Val489= (c.1467C>T) in the general population?

PRPF31 p.Val489= (c.1467C>T) is common (popmax 10.2%, sas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1467C>T · rs62144168 · VCV330111

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Common

common (popmax 10.2%, sas) — too common for a highly-penetrant pathogenic allele

Conditions

inherited retinal dystrophy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.264	benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.7	GERP -2.5, phastCons 1
Overall
CADD	11.69	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 10.2% South Asian · 9,285/91,086 alleles

Filtering AF 10% ClinGen BA1/BS1 input FAF95, joint · FAF99 9.95%

Overall 9.02% 145,514/1,613,984 alleles · common exomes 133,112/1,461,642 · genomes 12,402/152,342 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	10.2%	10
European (non-Finnish)	9.64%	10
Finnishnot grpmax-eligible	9.33%	11
Remaining individualsnot grpmax-eligible	8.83%	11
Middle Eastern	8%	12
African / African-American	6.75%	15
Ashkenazi Jewishnot grpmax-eligible	6.06%	17
Admixed American	5.89%	17
Amishnot grpmax-eligible	2.08%	48
East Asian	0.267%	374

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.Val489=
Coding: c.1467C>T
MANE Select: NM_015629
dbSNP: rs62144168
Type: single nucleotide variant
Location: chr19:54131399 (GRCh38)
Gene constraint: LOEUF 0.347 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 77.69 · 30 PDB

Full PRPF31 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

Also linked: retinitis pigmentosa 11 retinitis pigmentosa

Similar variants

PRPF31 c.1074-1G>C Likely pathogenic ★★ same condition
PRPF31 c.1074-2A>G Pathogenic ★★ same condition
PRPF31 c.1074-2A>T Pathogenic ★★ same condition
PRPF31 c.1146+5G>T Likely pathogenic ★★ same condition
PRPF31 c.1374+654C>G Pathogenic ★★ same condition
PRPF31 c.178-2A>G Pathogenic ★★ same condition
PRPF31 c.238+1G>A Pathogenic ★★ same condition
PRPF31 c.239-1G>A Pathogenic/Likely pathogenic ★★ 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-val489 (accessed [today's date]).

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