INTU p.Ala446=
c.1338G>A · rs771492553 · VCV2969311
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0111%, eas)
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 · G>T here scores Δ0.23 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -2.2 | GERP -4.2 |
| Overall | ||
| CADD | 2.319 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0111%
East Asian · 5/44,870 alleles
Filtering AF
0.00435%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00294%
Overall
0.00397%
64/1,613,362 alleles · ultra-rare
exomes 60/1,461,298 · genomes 4/152,064 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0111% | 8,974 |
| Remaining individualsnot grpmax-eligible | 0.00961% | 10,411 |
| European (non-Finnish) | 0.00424% | 23,593 |
| African / African-American | 0.00267% | 37,427 |
| South Asian | 0.0011% | 91,026 |
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
- INTU
- Protein
- p.Ala446=
- Coding
- c.1338G>A
- MANE Select
- NM_015693
- dbSNP
- rs771492553
- Type
- single nucleotide variant
- Location
- chr4:127687756 (GRCh38)
- Gene constraint
- LOEUF 1.012 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 67.35 · 4 PDB
- Residue 446
- a UniProt-annotated variant site (in srtd7/20; in an srtd7/20 patient who also carries variant wdr35 l-311); a UniProt-annotated variant site (in srtd20; loss of subcellular location to cilium basal body, when tested in a heterologous system); an α-helix
Similar variants
- INTU p.Ala611Thr Uncertain significance ★★ ⚠ same type
- INTU p.Ala804Val Uncertain significance ★★ ⚠ same type
- INTU p.Arg119Thr Uncertain significance ★★ ⚠ same type
- INTU p.Arg127Cys Uncertain significance ★★ ⚠ same type
- INTU p.Arg510Gln Uncertain significance ★★ ⚠ same type
- INTU p.Arg510Trp Uncertain significance ★★ ⚠ same type
- INTU p.Arg665Cys Uncertain significance ★★ ⚠ same type
- INTU p.Arg705Cys Uncertain significance ★★ ⚠ 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/intu-p-ala446 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown