TRAPPC12 p.Ser527=
c.1581C>T · rs199541864 · VCV2180889
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0187%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.036 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · C>G here scores Δ0.26 · evaluated, not missing |
| Constraint at this position | ||
| Conservation | phyloP 0.083 | GERP -1.4, phastCons 0.001 |
| Overall | ||
| CADD | 4.262 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0187%
European (non-Finnish) · 221/1,179,980 alleles
Filtering AF
0.0166%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0159%
Overall
0.0148%
239/1,611,356 alleles · ultra-rare
exomes 228/1,459,218 · genomes 11/152,138 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0187% | 5,339 |
| Middle Eastern | 0.0164% | 6,082 |
| Remaining individualsnot grpmax-eligible | 0.00961% | 10,410 |
| African / African-American | 0.00534% | 18,726 |
| Admixed American | 0.005% | 19,998 |
| Finnishnot grpmax-eligible | 0.00488% | 20,495 |
| South Asian | 0.0011% | 91,054 |
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
- TRAPPC12
- Protein
- p.Ser527=
- Coding
- c.1581C>T
- MANE Select
- NM_016030
- dbSNP
- rs199541864
- Type
- single nucleotide variant
- Location
- chr2:3457671 (GRCh38)
- Gene constraint
- LOEUF 1.192 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 68.52
Similar variants
- TRAPPC12 p.Ser527Asn Uncertain significance ★★ ⚠ same residue
- TRAPPC12 p.Ala627Val Pathogenic/Likely pathogenic ★★ same type
- TRAPPC12 c.1531-3C>T Uncertain significance ★★ same type
- TRAPPC12 c.1603+5G>C Uncertain significance ★★ same type
- TRAPPC12 p.Ala309Val Uncertain significance ★★ ⚠ same type
- TRAPPC12 p.Ala485Thr Uncertain significance ★★ ⚠ same type
- TRAPPC12 p.Ala637Val Uncertain significance ★★ ⚠ same type
- TRAPPC12 p.Arg166Ser 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/trappc12-p-ser527 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown