YTHDF1 p.Asn497=
c.1491C>T · rs111914412 · VCV720603
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
low-frequency (popmax 2.49%, 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 -6.5 | GERP -4 |
| Overall | ||
| CADD | 2.022 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
2.49%
African / African-American · 1,868/75,052 alleles
Filtering AF
2.39%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 2.36%
Overall
0.163%
2,636/1,614,264 alleles · low-frequency
exomes 1,519/1,461,894 · genomes 1,117/152,370 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 2.49% | 40 |
| Ashkenazi Jewishnot grpmax-eligible | 0.882% | 113 |
| Remaining individualsnot grpmax-eligible | 0.27% | 370 |
| Middle Eastern | 0.231% | 433 |
| Admixed American | 0.168% | 594 |
| Finnishnot grpmax-eligible | 0.0796% | 1,256 |
| East Asian | 0.0423% | 2,363 |
| European (non-Finnish) | 0.0122% | 8,195 |
| South Asian | 0.00988% | 10,121 |
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
- YTHDF1
- Protein
- p.Asn497=
- Coding
- c.1491C>T
- MANE Select
- NM_017798
- dbSNP
- rs111914412
- Type
- single nucleotide variant
- Location
- chr20:63202449 (GRCh38)
- Gene constraint
- LOEUF 0.515 · pLI 0.96 (gnomAD)
- Structure
- AlphaFold pLDDT 62.83 · 10 PDB
- Residue 497
- the yth domain; an α-helix
Similar variants
- YTHDF1 p.His375Tyr Benign ★★ same type
- YTHDF1 p.Lys473= Benign ★★ same type
- YTHDF1 p.Ser145= Benign ★★ same type
- YTHDF1 p.Ser252= Benign ★★ same type
- YTHDF1 p.Val195= Benign ★★ same type
- YTHDF1 p.Ala146Thr Uncertain significance ★ ⚠ same type
- YTHDF1 p.Ala199Ser Uncertain significance ★ ⚠ same type
- YTHDF1 p.Ala302Gly 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/ythdf1-p-asn497 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown