AACS p.Phe276=
c.828C>T · rs140471021 · VCV770614
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
low-frequency (popmax 3.23%, 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 -8 | GERP -3.6 |
| Overall | ||
| CADD | 4.951 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
3.23%
Admixed American · 1,936/60,018 alleles
Filtering AF
3.11%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 3.06%
Overall
0.154%
2,481/1,614,156 alleles · low-frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 3.23% | 31 |
| East Asian | 0.43% | 233 |
| Remaining individualsnot grpmax-eligible | 0.17% | 590 |
| African / African-American | 0.101% | 988 |
| South Asian | 0.045% | 2,221 |
| European (non-Finnish) | 0.0109% | 9,148 |
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.Phe276=
- Coding
- c.828C>T
- MANE Select
- NM_023928
- dbSNP
- rs140471021
- Type
- single nucleotide variant
- Location
- chr12:125107181 (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.Ala169Thr Uncertain significance ★ ⚠ same type
- AACS p.Ala271Pro Uncertain significance ★ ⚠ same type
- AACS p.Ala349Val Uncertain significance ★ ⚠ same type
- AACS p.Ala39Thr 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-phe276 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown