INTU p.Ser222=
c.666C>T · VCV3644430
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0407%, sas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -3.8 | GERP -2.3 |
| Overall | ||
| CADD | 9.864 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0407%
South Asian · 37/90,940 alleles
Filtering AF
0.0303%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0267%
Overall
0.0036%
58/1,612,010 alleles · ultra-rare
exomes 52/1,459,826 · genomes 6/152,184 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0407% | 2,458 |
| Remaining individualsnot grpmax-eligible | 0.00641% | 15,602 |
| African / African-American | 0.00267% | 37,444 |
| Admixed American | 0.00167% | 59,918 |
| European (non-Finnish) | 0.00119% | 84,180 |
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.Ser222=
- Coding
- c.666C>T
- MANE Select
- NM_015693
- Type
- single nucleotide variant
- Location
- chr4:127644040 (GRCh38)
- Gene constraint
- LOEUF 1.012 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 67.35 · 4 PDB
- Residue 222
- the pdz domain
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-ser222 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown