AACS p.Ser256=
c.768T>C · VCV4138950
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00559%, nfe)
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 -13 | GERP -3.3 |
| Overall | ||
| CADD | 0.038 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00559%
European (non-Finnish) · 66/1,180,018 alleles
Filtering AF
0.00451%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00411%
Overall
0.00446%
72/1,613,928 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00559% | 17,879 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,829 |
| Admixed American | 0.00333% | 30,002 |
| South Asian | 0.0011% | 91,088 |
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.Ser256=
- Coding
- c.768T>C
- MANE Select
- NM_023928
- Type
- single nucleotide variant
- Location
- chr12:125107121 (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-ser256 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown