AICDA p.Arg112=
c.336C>T · rs371372384 · VCV1125637
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00356%, nfe)
Conditions
1
hyper-IgM syndrome type 2
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.023 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
| Constraint at this position | ||
| Conservation | phyloP 2.1 | GERP 0.76, phastCons 1 |
| Overall | ||
| CADD | 10.28 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00356%
European (non-Finnish) · 42/1,180,052 alleles
Filtering AF
0.00267%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00236%
Overall
0.00291%
47/1,614,130 alleles · very rare
exomes 44/1,461,880 · genomes 3/152,250 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00356% | 28,096 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,244 |
| Admixed American | 0.00167% | 60,002 |
| African / African-American | 0.00133% | 74,952 |
| South Asian | 0.0011% | 91,092 |
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
- AICDA
- Protein
- p.Arg112=
- Coding
- c.336C>T
- MANE Select
- NM_020661
- dbSNP
- rs371372384
- Type
- single nucleotide variant
- Location
- chr12:8605306 (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 112
- the cmp/dcmp-type deaminase domain; the 'required for interaction with rnf126' region; a β-strand
Similar variants
- AICDA p.Arg112Cys Pathogenic ★★ same residue
- 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-arg112 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown