TULP1 p.Arg416=
c.1248T>C · rs540965177 · VCV2919105
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0174%, afr)
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 -3.4 | GERP -4.2 |
| Overall | ||
| CADD | 1.044 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0174%
African / African-American · 13/74,714 alleles
Filtering AF
0.0103%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00815%
Overall
0.000875%
14/1,599,792 alleles · ultra-rare
exomes 3/1,447,470 · genomes 11/152,322 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0174% | 5,747 |
| Admixed American | 0.00172% | 58,158 |
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.Arg416=
- Coding
- c.1248T>C
- MANE Select
- NM_003322
- dbSNP
- rs540965177
- Type
- single nucleotide variant
- Location
- chr6:35503634 (GRCh38)
- Gene constraint
- LOEUF 1.019 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 66.10 · 2 PDB
- Residue 416
- a β-strand
Similar variants
- TULP1 p.Arg416His Uncertain significance ★★ same residue
- TULP1 p.Arg416Leu Likely pathogenic ★ same residue
- TULP1 p.Arg416Cys Conflicting classifications of pathogenicity ★ ⚠ same residue
- TULP1 c.1112+1G>A Likely pathogenic ★★ same type
- TULP1 c.1495+1G>A Pathogenic/Likely pathogenic ★★ same type
- TULP1 c.1496-6C>A Pathogenic/Likely pathogenic ★★ same type
- TULP1 c.718+2T>C Pathogenic ★★ same type
- TULP1 c.99+1G>A Pathogenic/Likely pathogenic ★★ same type
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-arg416 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown