TSPEAR p.Phe606=
c.1818C>T · rs1205316092 · VCV2189440
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 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -2.5 | GERP -2.6 |
| Overall | ||
| CADD | 3.237 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00401%
African / African-American · 3/74,774 alleles
Filtering AF
0.00106%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000539%
Overall
0.00124%
20/1,613,568 alleles · very rare
exomes 14/1,461,724 · genomes 6/151,844 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00401% | 24,925 |
| East Asian | 0.00223% | 44,862 |
| South Asian | 0.0022% | 45,531 |
| European (non-Finnish) | 0.00119% | 84,277 |
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.Phe606=
- Coding
- c.1818C>T
- MANE Select
- NM_144991
- dbSNP
- rs1205316092
- Type
- single nucleotide variant
- Location
- chr21:44504818 (GRCh38)
- Gene constraint
- LOEUF 1.161 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 87.47
- Residue 606
- a UniProt-annotated variant site (in ectd14 and sthag10); a UniProt-annotated variant site (in ectd14); a UniProt-annotated variant site (in sthag10)
Similar variants
- 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
- TSPEAR p.Met1Thr 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-phe606 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown