FADS2 p.His221=
c.663C>T · rs149777687 · VCV780977
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.862%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -12 | GERP -4 |
| Overall | ||
| CADD | 2.058 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.862%
African / African-American · 647/75,042 alleles
Filtering AF
0.807%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.785%
Overall
0.0457%
737/1,614,196 alleles · rare
exomes 337/1,461,880 · genomes 400/152,316 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.862% | 116 |
| Middle Eastern | 0.0825% | 1,212 |
| Remaining individualsnot grpmax-eligible | 0.056% | 1,786 |
| Admixed American | 0.0283% | 3,531 |
| South Asian | 0.0132% | 7,590 |
| European (non-Finnish) | 0.00178% | 56,192 |
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
- FADS2
- Protein
- p.His221=
- Coding
- c.663C>T
- MANE Select
- NM_004265
- dbSNP
- rs149777687
- Type
- single nucleotide variant
- Location
- chr11:61848203 (GRCh38)
- Gene constraint
- LOEUF 0.415 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 95.39
Similar variants
- FADS2 p.Ala115Val Uncertain significance ★ ⚠ same type
- FADS2 p.Ala408Ser Uncertain significance ★ ⚠ same type
- FADS2 p.Arg14Cys Uncertain significance ★ ⚠ same type
- FADS2 p.Arg353His Uncertain significance ★ ⚠ same type
- FADS2 p.Arg58Gln Uncertain significance ★ ⚠ same type
- FADS2 p.Arg73Cys Uncertain significance ★ ⚠ same type
- FADS2 p.Asn156His Uncertain significance ★ ⚠ same type
- FADS2 p.Asn234Asp 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/fads2-p-his221 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown