TERF2IP p.Ala74=
c.222C>T · rs760403232 · VCV1788070
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.000347%, nfe)
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 -1.6 | GERP -1.3 |
| Overall | ||
| CADD | 11.66 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.000347%
European (non-Finnish) · 4/1,152,484 alleles
Filtering AF
8.1e-05%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 5.5e-05%
Overall
0.000257%
4/1,558,636 alleles · very rare
exomes 3/1,406,476 · genomes 1/152,160 · joint denominator
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
- TERF2IP
- Protein
- p.Ala74=
- Coding
- c.222C>T
- MANE Select
- NM_018975
- dbSNP
- rs760403232
- Type
- single nucleotide variant
- Location
- chr16:75648104 (GRCh38)
- Gene constraint
- LOEUF 1.45 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 72.76 · 5 PDB
Similar variants
- TERF2IP p.Ala123Gly Uncertain significance ★★ ⚠ same type
- TERF2IP p.Ala200Gly Uncertain significance ★★ ⚠ same type
- TERF2IP p.Ala387Val Uncertain significance ★★ ⚠ same type
- TERF2IP p.Ala61Thr Uncertain significance ★★ ⚠ same type
- TERF2IP p.Ala65Thr Uncertain significance ★★ ⚠ same type
- TERF2IP p.Arg133Gln Uncertain significance ★★ ⚠ same type
- TERF2IP p.Arg378Ser Uncertain significance ★★ ⚠ same type
- TERF2IP p.Arg392Gln 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/terf2ip-p-ala74 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown