KYNU p.Phe349=
c.1047T>C · rs114204731 · VCV716760
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
rare (popmax 0.479%, 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 0.71 | GERP 0.6, phastCons 1 |
| Overall | ||
| CADD | 8.81 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.479%
African / African-American · 359/74,948 alleles
Filtering AF
0.438%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.422%
Overall
0.024%
386/1,610,752 alleles · rare
exomes 181/1,458,568 · genomes 205/152,184 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.479% | 209 |
| Remaining individualsnot grpmax-eligible | 0.024% | 4,159 |
| Admixed American | 0.015% | 6,650 |
| European (non-Finnish) | 0.000255% | 392,418 |
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
- KYNU
- Protein
- p.Phe349=
- Coding
- c.1047T>C
- MANE Select
- NM_003937
- dbSNP
- rs114204731
- Type
- single nucleotide variant
- Location
- chr2:143040433 (GRCh38)
- Gene constraint
- LOEUF 1.364 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 95.55 · 3 PDB
- Residue 349
- a UniProt-annotated variant site (in vcrl2; strongly reduced 3-hydroxykynureninase activity); an α-helix
Similar variants
- KYNU p.Phe349fs Pathogenic/Likely pathogenic ★★ same residue
- KYNU c.902+1G>A Pathogenic/Likely pathogenic ★★ same type
- KYNU p.Arg428Trp Pathogenic/Likely pathogenic ★★ same type
- KYNU p.Trp109Ser Pathogenic/Likely pathogenic ★★ same type
- KYNU p.Tyr156Ter Pathogenic ★★ same type
- KYNU p.Arg358Gln Uncertain significance ★★ ⚠ same type
- KYNU p.Cys425Arg Uncertain significance ★★ ⚠ same type
- KYNU p.Met187Arg 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/kynu-p-phe349 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown