TULP1 p.Ala216=
c.648G>A · rs766865255 · VCV1140272
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0424%, eas)
Conditions
1
inherited retinal dystrophy
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · C>A here scores Δ0.27 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 0.67 | GERP -0.5, phastCons 0.37 |
| Overall | ||
| CADD | 5.443 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0424%
East Asian · 19/44,854 alleles
Filtering AF
0.0277%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.023%
Overall
0.00285%
46/1,613,980 alleles · ultra-rare
exomes 42/1,461,890 · genomes 4/152,090 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0424% | 2,361 |
| European (non-Finnish) | 0.00212% | 47,201 |
| Admixed American | 0.00167% | 59,976 |
| South Asian | 0.0011% | 91,088 |
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
- TULP1
- Protein
- p.Ala216=
- Coding
- c.648G>A
- MANE Select
- NM_003322
- dbSNP
- rs766865255
- Type
- single nucleotide variant
- Location
- chr6:35509704 (GRCh38)
- Gene constraint
- LOEUF 1.019 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 66.10 · 2 PDB
- Residue 216
- the 'disordered' region
Similar variants
- TULP1 p.Ala216Val Uncertain significance ★★ ⚠ same residue
- TULP1 p.Ala216Gly Uncertain significance ★ ⚠ same residue
- TULP1 c.1496-6C>A Pathogenic/Likely pathogenic ★★ same condition
- TULP1 c.718+2T>C Pathogenic ★★ same condition
- TULP1 p.Arg361Ter Pathogenic ★★ same condition
- TULP1 p.Arg400Trp Pathogenic/Likely pathogenic ★★ same condition
- TULP1 p.Arg419Trp Pathogenic/Likely pathogenic ★★ same condition
- TULP1 p.Arg440Ter 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/tulp1-p-ala216 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown