TERF2IP p.Ala351=
c.1053G>A · rs200023051 · VCV1777883
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0156%, eas)
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 0.41 | GERP -3.8, phastCons 0.98 |
| Overall | ||
| CADD | 8.007 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0156%
East Asian · 7/44,886 alleles
Filtering AF
0.00726%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00514%
Overall
0.00341%
55/1,614,184 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0156% | 6,412 |
| Remaining individualsnot grpmax-eligible | 0.0064% | 15,627 |
| South Asian | 0.00439% | 22,769 |
| African / African-American | 0.004% | 25,016 |
| European (non-Finnish) | 0.00305% | 32,778 |
| Admixed American | 0.00167% | 60,032 |
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.Ala351=
- Coding
- c.1053G>A
- MANE Select
- NM_018975
- dbSNP
- rs200023051
- Type
- single nucleotide variant
- Location
- chr16:75656464 (GRCh38)
- Gene constraint
- LOEUF 1.45 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 72.76 · 5 PDB
- Residue 351
- an α-helix
Similar variants
- TERF2IP p.Ala351Val Uncertain significance ★ ⚠ same residue
- 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
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-ala351 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown