FYN p.Pro488=
c.1464G>A · VCV4027439
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0267%, amr)
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 -4.4 | GERP -5.7 |
| Overall | ||
| CADD | 7.045 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0267%
Admixed American · 16/60,016 alleles
Filtering AF
0.0166%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0136%
Overall
0.00384%
62/1,614,060 alleles · ultra-rare
exomes 54/1,461,792 · genomes 8/152,268 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0267% | 3,751 |
| Middle Eastern | 0.0165% | 6,062 |
| African / African-American | 0.00666% | 15,005 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,254 |
| European (non-Finnish) | 0.00314% | 31,891 |
| South Asian | 0.0011% | 91,074 |
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
- FYN
- Protein
- p.Pro488=
- Coding
- c.1464G>A
- MANE Select
- NM_002037
- Type
- single nucleotide variant
- Location
- chr6:111661889 (GRCh38)
- Gene constraint
- LOEUF 0.215 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 81.62 · 53 PDB
- Residue 488
- the protein kinase domain; an α-helix
Similar variants
- FYN p.Asp506Glu Benign ★★ same type
- FYN c.344+1G>A Uncertain significance ★ same type
- FYN p.Ala55Thr Uncertain significance ★ ⚠ same type
- FYN p.Arg123Cys Uncertain significance ★ ⚠ same type
- FYN p.Arg161Ter Uncertain significance ★ same type
- FYN p.Arg29Cys Uncertain significance ★ ⚠ same type
- FYN p.Asp8Glu Uncertain significance ★ ⚠ same type
- FYN p.Asp92Asn 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/fyn-p-pro488 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown