AHR p.Phe659=
c.1977C>T · rs139422560 · VCV1984756
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.02%, 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 -11 | GERP -3.8 |
| Overall | ||
| CADD | 0.061 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.02%
African / African-American · 15/74,926 alleles
Filtering AF
0.0123%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00989%
Overall
0.00136%
22/1,614,044 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.02% | 4,995 |
| Middle Eastern | 0.0164% | 6,084 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,241 |
| Admixed American | 0.00167% | 59,998 |
| Finnishnot grpmax-eligible | 0.00156% | 64,030 |
| South Asian | 0.0011% | 91,078 |
| European (non-Finnish) | 8.47e-05% | 1,180,040 |
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
- AHR
- Protein
- p.Phe659=
- Coding
- c.1977C>T
- MANE Select
- NM_001621
- dbSNP
- rs139422560
- Type
- single nucleotide variant
- Location
- chr7:17339802 (GRCh38)
- Gene constraint
- LOEUF 0.606 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 56.88 · 3 PDB
- Residue 659
- a UniProt-annotated variant site (in fvh3; likely pathogenic; decreased protein abundance in homozygous patient cells; results in decreased ligand-activated transcription activator activity; cyp1a1 and cyp1b1 expression levels in homozygous patient cells treated with benzanthracene are reduced compared to controls)
Similar variants
- AHR p.Ala313Thr Uncertain significance ★★ ⚠ same type
- AHR p.Ala459Ser Uncertain significance ★★ ⚠ same type
- AHR p.Arg352Trp Uncertain significance ★★ ⚠ same type
- AHR p.Asn179His Uncertain significance ★★ ⚠ same type
- AHR p.Asn238Ser Uncertain significance ★★ ⚠ same type
- AHR p.Asn789Ser Uncertain significance ★★ ⚠ same type
- AHR p.Asp841Asn Uncertain significance ★★ ⚠ same type
- AHR p.Gln113His 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/ahr-p-phe659 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown