INTU p.Ser674=
c.2022G>A · rs147052791 · VCV1933079
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0165%, mid)
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>C here scores Δ0.22 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -1.2 | GERP -3.3 |
| Overall | ||
| CADD | 6.945 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0165%
Middle Eastern · 1/6,058 alleles
Filtering AF
0.00741%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00692%
Overall
0.00731%
118/1,614,042 alleles · ultra-rare
exomes 115/1,461,768 · genomes 3/152,274 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0165% | 6,058 |
| East Asian | 0.00891% | 11,219 |
| European (non-Finnish) | 0.00881% | 11,346 |
| Remaining individualsnot grpmax-eligible | 0.0064% | 15,626 |
| African / African-American | 0.004% | 25,009 |
| South Asian | 0.0022% | 45,539 |
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.Ser674=
- Coding
- c.2022G>A
- MANE Select
- NM_015693
- dbSNP
- rs147052791
- Type
- single nucleotide variant
- Location
- chr4:127706720 (GRCh38)
- Gene constraint
- LOEUF 1.012 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 67.35 · 4 PDB
- Residue 674
- 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); a modified residue (phosphoserine)
Similar variants
- INTU p.Ser674Leu Uncertain significance ★ ⚠ same residue
- 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
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-ser674 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown