Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
low-frequency (popmax 3.95%, afr)
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 7.4 | GERP -5.2, phastCons 1 |
| Overall | ||
| CADD | 11.95 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
3.95%
African / African-American · 2,967/75,030 alleles
Filtering AF
3.84%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 3.79%
Overall
0.207%
3,348/1,614,188 alleles · low-frequency
exomes 1,628/1,461,872 · genomes 1,720/152,316 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 3.95% | 25 |
| Admixed American | 0.26% | 385 |
| Middle Eastern | 0.248% | 403 |
| Remaining individualsnot grpmax-eligible | 0.246% | 406 |
| South Asian | 0.00878% | 11,385 |
| European (non-Finnish) | 0.00407% | 24,584 |
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
- S100A4
- Protein
- p.Phe78=
- Coding
- c.234C>T
- MANE Select
- NM_002961
- dbSNP
- rs9003
- Type
- single nucleotide variant
- Location
- chr1:153543831 (GRCh38)
- Gene constraint
- LOEUF 1.13 · pLI 0.16 (gnomAD)
- Structure
- AlphaFold pLDDT 86.09 · 18 PDB
- Residue 78
- an α-helix; the ef-hand 2 domain
Similar variants
- S100A4 p.Asn61= Benign ★★ same type
- S100A4 p.Ser20= Benign ★★ same type
- S100A4 p.Arg40Gln Uncertain significance ★ ⚠ same type
- S100A4 p.Asp95Asn Uncertain significance ★ ⚠ same type
- S100A4 p.Gln97Pro Uncertain significance ★ ⚠ same type
- S100A4 p.Glu69Lys Uncertain significance ★ ⚠ same type
- S100A4 p.Gly47Arg Uncertain significance ★ ⚠ same type
- S100A4 p.Met84Leu 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/s100a4-p-phe78 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown