AFG3L2 c.1663+273G>A
Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Common
common (popmax 22.1%, eas) — 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 | ||
| Splice region | donor +273 | deep intronic (+273 nt into the intron) |
|---|---|---|
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -2.2 | GERP -0.58 |
| Non-coding constraint | Z 1.65 | 1 kb window · o/e 0.87 · regional · uncalibrated |
| Overall | ||
| CADD | 0.272 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
22.1%
East Asian · 1,146/5,182 alleles
Filtering AF
21.1%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 20.6%
Overall
11%
16,716/152,210 alleles · common
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 22.1% | 5 |
| Admixed American | 18.8% | 5 |
| Remaining individualsnot grpmax-eligible | 10.5% | 10 |
| Amishnot grpmax-eligible | 10.3% | 10 |
| European (non-Finnish) | 10.1% | 10 |
| African / African-American | 9.55% | 10 |
| South Asian | 9.39% | 11 |
| Ashkenazi Jewishnot grpmax-eligible | 9% | 11 |
| Finnishnot grpmax-eligible | 7% | 14 |
| Middle Eastern | 5.78% | 17 |
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
- AFG3L2
- Coding
- c.1663+273G>A
- MANE Select
- NM_006796
- dbSNP
- rs7229258
- Type
- single nucleotide variant
- Location
- chr18:12348000 (GRCh38)
- Gene constraint
- LOEUF 0.724 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 77.07 · 2 PDB
Similar variants
- AFG3L2 p.Arg41Ter Pathogenic/Likely pathogenic ★★ same type
- AFG3L2 p.Arg468Cys Pathogenic/Likely pathogenic ★★ same type
- AFG3L2 p.Arg68Ter Pathogenic ★★ same type
- AFG3L2 p.Gly337Glu Pathogenic ★★ same type
- AFG3L2 p.Gly385Ser Likely pathogenic ★★ same type
- AFG3L2 p.Gly671Arg Pathogenic ★★ same type
- AFG3L2 p.Met666Thr Pathogenic/Likely pathogenic ★★ same type
- AFG3L2 p.Met666Val Pathogenic/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/afg3l2-c-1663-plus-273g-a (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown