ADGRF5 p.Ser494=
c.1482T>C · VCV4820918
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.814%, 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 -0.57 | GERP -3.6 |
| Overall | ||
| CADD | 7.344 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.814%
African / African-American · 611/75,022 alleles
Filtering AF
0.761%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.74%
Overall
0.0424%
684/1,613,558 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.814% | 123 |
| Middle Eastern | 0.0825% | 1,212 |
| Admixed American | 0.0466% | 2,144 |
| Remaining individualsnot grpmax-eligible | 0.0464% | 2,155 |
| South Asian | 0.00769% | 13,008 |
| European (non-Finnish) | 0.000339% | 294,870 |
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
- ADGRF5
- Protein
- p.Ser494=
- Coding
- c.1482T>C
- MANE Select
- NM_001098518
- Type
- single nucleotide variant
- Location
- chr6:46869022 (GRCh38)
- Gene constraint
- LOEUF 0.719 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 74.74
- Residue 494
- the ig-like 3 domain; a disulfide bond
Similar variants
- ADGRF5 p.Ala1064Val Uncertain significance ★ ⚠ same type
- ADGRF5 p.Ala1072Thr Uncertain significance ★ ⚠ same type
- ADGRF5 p.Ala1072Val Uncertain significance ★ ⚠ same type
- ADGRF5 p.Ala1088Ser Uncertain significance ★ ⚠ same type
- ADGRF5 p.Ala1179Glu Uncertain significance ★ ⚠ same type
- ADGRF5 p.Ala268Thr Uncertain significance ★ ⚠ same type
- ADGRF5 p.Ala324Val Uncertain significance ★ ⚠ same type
- ADGRF5 p.Ala457Thr 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/adgrf5-p-ser494 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown