EEFSEC p.Pro180=
c.540G>A · rs116353475 · VCV775907
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Common
common (popmax 5.1%, afr) — too common for a highly-penetrant pathogenic allele
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 | GERP -4.5 |
| Overall | ||
| CADD | 0.837 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
5.1%
African / African-American · 3,825/74,992 alleles
Filtering AF
4.97%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 4.91%
Overall
0.281%
4,539/1,614,084 alleles · common
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 5.1% | 20 |
| Admixed American | 0.41% | 244 |
| Remaining individualsnot grpmax-eligible | 0.382% | 262 |
| Middle Eastern | 0.33% | 303 |
| South Asian | 0.0231% | 4,337 |
| European (non-Finnish) | 0.0158% | 6,344 |
| East Asian | 0.00446% | 22,437 |
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
- EEFSEC
- Protein
- p.Pro180=
- Coding
- c.540G>A
- MANE Select
- NM_021937
- dbSNP
- rs116353475
- Type
- single nucleotide variant
- Location
- chr3:128262143 (GRCh38)
- Gene constraint
- LOEUF 1.345 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 79.98 · 4 PDB
- Residue 180
- the tr-type g domain
Similar variants
- EEFSEC p.Pro180Leu Uncertain significance ★ ⚠ same residue
- EEFSEC p.Arg285Gln Uncertain significance ★★ ⚠ same type
- EEFSEC p.Arg424Gln Uncertain significance ★★ ⚠ same type
- EEFSEC p.Phe463Leu Uncertain significance ★★ ⚠ same type
- EEFSEC p.Ala435Val Benign ★★ same type
- EEFSEC p.Phe581Cys Benign ★★ same type
- EEFSEC p.Asp390Ala Likely pathogenic ★ ⚠ same type
- EEFSEC p.Glu514Ter Likely pathogenic ★ 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/eefsec-p-pro180 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown