EXOC2 p.Pro8=
c.24C>G · rs148665259 · VCV2656170
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.792%, mid)
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 -9.7 | GERP -5 |
| Overall | ||
| CADD | 0.208 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.792%
Middle Eastern · 48/6,058 alleles
Filtering AF
0.614%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.551%
Overall
0.11%
1,773/1,613,802 alleles · rare
exomes 1,623/1,461,458 · genomes 150/152,344 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.792% | 126 |
| South Asian | 0.18% | 555 |
| Remaining individualsnot grpmax-eligible | 0.125% | 801 |
| European (non-Finnish) | 0.12% | 836 |
| Admixed American | 0.0617% | 1,620 |
| Finnishnot grpmax-eligible | 0.0312% | 3,201 |
| African / African-American | 0.0173% | 5,772 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00676% | 14,800 |
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
- EXOC2
- Protein
- p.Pro8=
- Coding
- c.24C>G
- MANE Select
- NM_018303
- dbSNP
- rs148665259
- Type
- single nucleotide variant
- Location
- chr6:637795 (GRCh38)
- Gene constraint
- LOEUF 0.626 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 80.82
- Residue 8
- the ipt/tig domain
Similar variants
- EXOC2 p.Arg414His Uncertain significance ★★ ⚠ same type
- EXOC2 p.Asp892Glu Uncertain significance ★★ ⚠ same type
- EXOC2 p.Leu458= Likely benign ★★ same type
- EXOC2 p.Phe153= Likely benign ★★ same type
- EXOC2 c.1443+10C>T Uncertain significance ★ same type
- EXOC2 c.1932+4A>C Uncertain significance ★ same type
- EXOC2 p.Ala228Thr Uncertain significance ★ ⚠ same type
- EXOC2 p.Ala425Val 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/exoc2-p-pro8 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown