EEFSEC p.Ala128=
c.384G>A · VCV4246808
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0164%, 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 -9.1 | GERP -4.5 |
| Overall | ||
| CADD | 0.214 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0164%
Middle Eastern · 1/6,084 alleles
Filtering AF
0.00255%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00161%
Overall
0.000558%
9/1,614,092 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0164% | 6,084 |
| African / African-American | 0.00667% | 14,986 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,488 |
| South Asian | 0.0011% | 91,092 |
| European (non-Finnish) | 8.47e-05% | 1,180,048 |
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.Ala128=
- Coding
- c.384G>A
- MANE Select
- NM_021937
- Type
- single nucleotide variant
- Location
- chr3:128246903 (GRCh38)
- Gene constraint
- LOEUF 1.345 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 79.98 · 4 PDB
- Residue 128
- the tr-type g domain; an α-helix
Similar variants
- 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.Pro180= 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-ala128 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown