F5 p.Asn554=
c.1662C>T · rs376310610 · VCV1777515
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00223%, eas)
Conditions
2
Inborn genetic diseases
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 4.5 | GERP 1, phastCons 1 |
| Overall | ||
| CADD | 8.511 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00223%
East Asian · 1/44,896 alleles
Filtering AF
0.000763%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000605%
Overall
0.00112%
18/1,613,994 alleles · very rare
exomes 16/1,461,852 · genomes 2/152,142 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.00223% | 44,896 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,488 |
| Finnishnot grpmax-eligible | 0.00156% | 64,010 |
| European (non-Finnish) | 0.00127% | 78,667 |
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
- F5
- Protein
- p.Asn554=
- Coding
- c.1662C>T
- MANE Select
- NM_000130
- dbSNP
- rs376310610
- Type
- single nucleotide variant
- Location
- chr1:169546542 (GRCh38)
- Gene constraint
- LOEUF 0.704 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 62.57 · 23 PDB
- Residue 554
- the plastocyanin-like 4 domain; a turn; the f5/8 type a 2 domain
Similar variants
- F5 c.1297-2A>G Pathogenic/Likely pathogenic ★★ same condition
- F5 p.Arg1030Ter Pathogenic ★★ same condition
- F5 p.Arg146Ter Pathogenic/Likely pathogenic ★★ same condition
- F5 p.Arg1621Ter Pathogenic/Likely pathogenic ★★ same condition
- F5 p.Arg1634Ter Pathogenic/Likely pathogenic ★★ same condition
- F5 p.Arg2102His Pathogenic/Likely pathogenic ★★ same condition
- F5 p.Arg740Ter Pathogenic/Likely pathogenic ★★ same condition
- F5 p.Asp96His Pathogenic ★★ same condition
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/f5-p-asn554 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown