INTU p.Ser451=
c.1353C>T · VCV4749857
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00401%, afr)
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>G here scores Δ0.29 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -2.5 | GERP -3.5 |
| Overall | ||
| CADD | 2.567 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00401%
African / African-American · 3/74,892 alleles
Filtering AF
0.00106%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00065%
Overall
0.0013%
21/1,613,290 alleles · very rare
exomes 19/1,461,144 · genomes 2/152,146 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00401% | 24,964 |
| Admixed American | 0.00167% | 59,914 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,440 |
| European (non-Finnish) | 0.00136% | 73,723 |
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.Ser451=
- Coding
- c.1353C>T
- MANE Select
- NM_015693
- Type
- single nucleotide variant
- Location
- chr4:127687771 (GRCh38)
- Gene constraint
- LOEUF 1.012 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 67.35 · 4 PDB
- Residue 451
- 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)
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-ser451 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown