AICDA p.Phe109Ser
c.326T>C · VCV4691420
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
AlphaMissense
likely pathogenic
0.9718 · ACMG-weighted
gnomAD v4.1
Absent
absent from gnomAD v4.1
Missense predictors
2/3 damaging
AlphaMissense, REVEL, SaProt
Conditions
1
hyper-IgM syndrome type 2
Computational evidence
| Protein change | ||
| AlphaMissense | 0.9718 | likely pathogenic |
|---|---|---|
| REVEL | 0.798 | moderately pathogenic-leaning |
| SaProt | LLR -8.68 | tolerated |
| ⇒ AlphaMissense and REVEL call this damaging; SaProt does not. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 9.2 | GERP 1.7, phastCons 1 |
| Regional constraint | o/e 0.86 | unconstrained · MANE · 8,480 bp · p 0.018 · regional, not allelic |
| Overall | ||
| CADD | 28.3 | PHRED · no single calibrated threshold — expert panels disagree |
AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.
Population frequency
gnomAD v4.1 · exomes + genomes
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- AICDA
- Protein
- p.Phe109Ser
- Coding
- c.326T>C
- MANE Select
- NM_020661
- Type
- single nucleotide variant
- Location
- chr12:8605316 (GRCh38)
- Gene constraint
- LOEUF 1.144 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 88.43 · 5 PDB
- Residue 109
- the cmp/dcmp-type deaminase domain; the 'required for interaction with rnf126' region; a β-strand
Similar variants
- AICDA p.Arg112Cys Pathogenic ★★ same condition
- AICDA p.Arg190Ter Pathogenic/Likely pathogenic ★★ same condition
- AICDA p.Arg24Trp Pathogenic ★★ same condition
- AICDA p.Arg92Ter Pathogenic/Likely pathogenic ★★ same condition
- AICDA p.Arg99Ter Pathogenic/Likely pathogenic ★★ same condition
- AICDA p.Cys147Ter Pathogenic ★★ same condition
- AICDA p.Cys87Arg Pathogenic/Likely pathogenic ★★ ⚠ same condition
- AICDA p.Cys87Ser Pathogenic/Likely 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/aicda-p-phe109ser (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown