FOXI3 p.Ser418=
c.1254C>T · rs897006327 · VCV2756224
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00137%, afr)
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 -4.7 | GERP -3.7 |
| Overall | ||
| CADD | 0.341 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00137%
African / African-American · 1/72,968 alleles
Filtering AF
0.000188%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000124%
Overall
0.000451%
7/1,551,174 alleles · very rare
exomes 6/1,399,160 · genomes 1/152,014 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00137% | 72,968 |
| European (non-Finnish) | 0.000523% | 191,149 |
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
- FOXI3
- Protein
- p.Ser418=
- Coding
- c.1254C>T
- MANE Select
- NM_001135649
- dbSNP
- rs897006327
- Type
- single nucleotide variant
- Location
- chr2:88448216 (GRCh38)
- Gene constraint
- LOEUF 0.73 · pLI 0.65 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 59.00
- Residue 418
- a UniProt-annotated variant site (in cfm2; decreased transcription factor activity; does not affect localization to the nucleus)
Similar variants
- FOXI3 p.Arg236Trp Likely pathogenic ★★ same type
- FOXI3 p.Ala71Pro Uncertain significance ★★ ⚠ same type
- FOXI3 p.Arg238Ter Uncertain significance ★★ same type
- FOXI3 p.Arg241Cys Uncertain significance ★★ ⚠ same type
- FOXI3 p.Asp212Glu Uncertain significance ★★ ⚠ same type
- FOXI3 p.Cys5Tyr Uncertain significance ★★ ⚠ same type
- FOXI3 p.Glu163Lys Uncertain significance ★★ ⚠ same type
- FOXI3 p.Gly38Ala 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/foxi3-p-ser418 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown