TSPEAR p.Phe199=
c.597C>T · rs377364549 · VCV1584304
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00333%, amr)
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 1.4 | GERP -1.1, phastCons 0.89 |
| Overall | ||
| CADD | 9.603 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00333%
Admixed American · 2/59,998 alleles
Filtering AF
0.00153%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0013%
Overall
0.00192%
31/1,613,632 alleles · very rare
exomes 29/1,461,470 · genomes 2/152,162 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00333% | 29,999 |
| African / African-American | 0.00267% | 37,454 |
| East Asian | 0.00223% | 44,894 |
| European (non-Finnish) | 0.0022% | 45,385 |
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
- TSPEAR
- Protein
- p.Phe199=
- Coding
- c.597C>T
- MANE Select
- NM_144991
- dbSNP
- rs377364549
- Type
- single nucleotide variant
- Location
- chr21:44531079 (GRCh38)
- Gene constraint
- LOEUF 1.161 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 87.47
- Residue 199
- the laminin g-like domain; a UniProt-annotated variant site (in ectd14 and sthag10)
Similar variants
- TSPEAR p.Phe199Val Uncertain significance ★★ ⚠ same residue
- TSPEAR c.1336+2T>A Pathogenic/Likely pathogenic ★★ same type
- TSPEAR c.1337-2A>G Likely pathogenic ★★ same type
- TSPEAR c.1856+2T>C Pathogenic/Likely pathogenic ★★ same type
- TSPEAR p.Arg144Ter Pathogenic ★★ same type
- TSPEAR p.Arg197Ter Pathogenic/Likely pathogenic ★★ same type
- TSPEAR p.Gln365Ter Pathogenic ★★ same type
- TSPEAR p.Gln79Ter Pathogenic/Likely pathogenic ★★ 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/tspear-p-phe199 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown