INTU p.Pro583=
c.1749G>A · rs201612700 · VCV2154870
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.338%, sas)
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 | GERP -1.9, phastCons 1 |
| Overall | ||
| CADD | 13.23 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.338%
South Asian · 308/91,074 alleles
Filtering AF
0.307%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.295%
Overall
0.0255%
412/1,613,994 alleles · rare
exomes 386/1,461,728 · genomes 26/152,266 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.338% | 296 |
| Remaining individualsnot grpmax-eligible | 0.0288% | 3,473 |
| Middle Eastern | 0.0165% | 6,062 |
| European (non-Finnish) | 0.00678% | 14,749 |
| African / African-American | 0.00533% | 18,755 |
| East Asian | 0.00223% | 44,872 |
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.Pro583=
- Coding
- c.1749G>A
- MANE Select
- NM_015693
- dbSNP
- rs201612700
- Type
- single nucleotide variant
- Location
- chr4:127705773 (GRCh38)
- Gene constraint
- LOEUF 1.012 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 67.35 · 4 PDB
- Residue 583
- 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-pro583 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown