FAP p.Tyr458=
c.1374C>T · rs62001030 · VCV714963
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.971%, 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 -0.23 | GERP -5.7, phastCons 0.014 |
| Overall | ||
| CADD | 7.529 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.971%
African / African-American · 729/75,042 alleles
Filtering AF
0.913%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.89%
Overall
0.0548%
884/1,614,066 alleles · rare
exomes 435/1,461,768 · genomes 449/152,298 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.971% | 103 |
| Admixed American | 0.09% | 1,111 |
| Remaining individualsnot grpmax-eligible | 0.0832% | 1,202 |
| Middle Eastern | 0.0495% | 2,020 |
| South Asian | 0.0198% | 5,060 |
| European (non-Finnish) | 0.00237% | 42,140 |
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
- FAP
- Protein
- p.Tyr458=
- Coding
- c.1374C>T
- MANE Select
- NM_004460
- dbSNP
- rs62001030
- Type
- single nucleotide variant
- Location
- chr2:162198785 (GRCh38)
- Gene constraint
- LOEUF 0.892 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 95.72 · 4 PDB
- Residue 458
- an α-helix
Similar variants
- FAP c.1870-8C>A Benign ★★ same type
- FAP p.Ala100= Benign ★★ same type
- FAP p.Gln708= Benign ★★ same type
- FAP p.Gly195= Benign ★★ same type
- FAP p.Leu212Phe Benign ★★ same type
- FAP p.Phe185Leu Likely benign ★★ same type
- FAP p.Ser737= Likely benign ★★ same type
- FAP p.Thr229Met Benign ★★ ⚠ 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/fap-p-tyr458 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown