PRPF6 p.Ala648=
c.1944C>T · rs151332876 · VCV339480
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
rare (popmax 0.187%, eas)
Conditions
2
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 -12 | GERP -4 |
| Overall | ||
| CADD | 1.331 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.187%
East Asian · 84/44,886 alleles
Filtering AF
0.155%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.143%
Overall
0.0176%
284/1,613,514 alleles · rare
exomes 259/1,461,148 · genomes 25/152,366 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.187% | 534 |
| Remaining individualsnot grpmax-eligible | 0.0336% | 2,976 |
| Admixed American | 0.0267% | 3,751 |
| Middle Eastern | 0.0165% | 6,062 |
| European (non-Finnish) | 0.0122% | 8,195 |
| African / African-American | 0.012% | 8,341 |
| Finnishnot grpmax-eligible | 0.0111% | 9,046 |
| South Asian | 0.0022% | 45,544 |
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
- PRPF6
- Protein
- p.Ala648=
- Coding
- c.1944C>T
- MANE Select
- NM_012469
- dbSNP
- rs151332876
- Type
- single nucleotide variant
- Location
- chr20:64025974 (GRCh38)
- Gene constraint
- LOEUF 0.445 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 80.07 · 33 PDB
- Residue 648
- an α-helix
Similar variants
- PRPF6 p.Ala65Thr Uncertain significance ★★ ⚠ same condition
- PRPF6 p.Arg703Trp Uncertain significance ★★ ⚠ same condition
- PRPF6 p.His368Arg Uncertain significance ★★ ⚠ same condition
- PRPF6 p.Ile919Val Uncertain significance ★★ ⚠ same condition
- PRPF6 p.Pro282Leu Uncertain significance ★★ ⚠ same condition
- PRPF6 p.Val411Ile Uncertain significance ★★ ⚠ same condition
- PRPF6 c.1186+13C>T Benign/Likely benign ★★ same condition
- PRPF6 c.2340-11T>C 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/prpf6-p-ala648 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown