TECPR2 p.Pro1372=
c.4116G>A · rs777406369 · VCV1145656
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.035%, amr)
Conditions
2
hereditary spastic paraplegia
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 -2.1 | GERP -3.3 |
| Overall | ||
| CADD | 3.988 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.035%
Admixed American · 21/59,976 alleles
Filtering AF
0.0234%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0197%
Overall
0.0036%
58/1,613,170 alleles · ultra-rare
exomes 43/1,461,140 · genomes 15/152,030 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.035% | 2,856 |
| African / African-American | 0.0227% | 4,406 |
| Remaining individualsnot grpmax-eligible | 0.008% | 12,496 |
| South Asian | 0.0022% | 45,532 |
| European (non-Finnish) | 0.0011% | 90,766 |
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
- TECPR2
- Protein
- p.Pro1372=
- Coding
- c.4116G>A
- MANE Select
- NM_014844
- dbSNP
- rs777406369
- Type
- single nucleotide variant
- Location
- chr14:102498137 (GRCh38)
- Gene constraint
- LOEUF 0.607 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 68.27
Similar variants
- TECPR2 p.Pro1372Arg Uncertain significance ⚠ same residue
- TECPR2 p.Pro1372Ser Uncertain significance ★ ⚠ same residue
- TECPR2 c.1084+2T>C Likely pathogenic ★★ same condition
- TECPR2 c.1418-2A>G Likely pathogenic ★★ same condition
- TECPR2 c.2753-1G>A Likely pathogenic ★★ same condition
- TECPR2 p.Gln1189Ter Pathogenic/Likely pathogenic ★★ same condition
- TECPR2 p.Gln191Ter Pathogenic/Likely pathogenic ★★ same condition
- TECPR2 p.Gln852Ter Pathogenic ★★ same condition
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/tecpr2-p-pro1372 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown