AACS p.Ser554=
c.1662G>A · rs143787385 · VCV726069
Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.905%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.026 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -5.6 | GERP -3.3 |
| Overall | ||
| CADD | 5.849 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.905%
African / African-American · 679/74,992 alleles
Filtering AF
0.849%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.826%
Overall
0.0476%
769/1,614,098 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.905% | 110 |
| Remaining individualsnot grpmax-eligible | 0.064% | 1,563 |
| Admixed American | 0.0433% | 2,309 |
| Middle Eastern | 0.0165% | 6,062 |
| South Asian | 0.00439% | 22,769 |
| European (non-Finnish) | 0.00161% | 62,106 |
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
- AACS
- Protein
- p.Ser554=
- Coding
- c.1662G>A
- MANE Select
- NM_023928
- dbSNP
- rs143787385
- Type
- single nucleotide variant
- Location
- chr12:125134836 (GRCh38)
- Gene constraint
- LOEUF 0.967 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 92.09
Similar variants
- AACS c.1881+8C>G Benign ★★ same type
- AACS p.Arg107= Benign ★★ same type
- AACS p.Glu564Gln Benign ★★ same type
- AACS p.Ile430= Benign ★★ same type
- AACS p.Phe276= Benign ★★ same type
- AACS p.Ala169Thr Uncertain significance ★ ⚠ same type
- AACS p.Ala271Pro Uncertain significance ★ ⚠ same type
- AACS p.Ala349Val 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/aacs-p-ser554 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown