EFL1 p.Pro492=
c.1476T>C · rs576437556 · VCV2730469
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00667%, afr)
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 -0.11 | |
| Overall | ||
| CADD | 3.426 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00667%
African / African-American · 5/74,986 alleles
Filtering AF
0.00255%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00161%
Overall
0.00093%
15/1,613,318 alleles · very rare
exomes 10/1,461,014 · genomes 5/152,304 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00667% | 14,997 |
| South Asian | 0.0011% | 90,812 |
| European (non-Finnish) | 0.000763% | 131,089 |
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
- EFL1
- Protein
- p.Pro492=
- Coding
- c.1476T>C
- MANE Select
- NM_024580
- dbSNP
- rs576437556
- Type
- single nucleotide variant
- Location
- chr15:82219787 (GRCh38)
- Gene constraint
- LOEUF 0.718 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 74.72 · 2 PDB
- Residue 492
- the 'disordered' region
Similar variants
- EFL1 p.Pro492Ser Uncertain significance ★★ ⚠ same residue
- EFL1 p.Pro492Ala Uncertain significance ★ ⚠ same residue
- EFL1 c.1444+3A>C Uncertain significance ★★ same type
- EFL1 c.244+2T>G Uncertain significance ★★ same type
- EFL1 p.Ala755Thr Uncertain significance ★★ ⚠ same type
- EFL1 p.Arg108His Uncertain significance ★★ ⚠ same type
- EFL1 p.Arg1097Trp Uncertain significance ★★ ⚠ same type
- EFL1 p.Arg330Trp 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/efl1-p-pro492 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown