AICDA p.Arg127=
c.379C>A · rs141451637 · VCV463869
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.129%, afr)
Conditions
1
hyper-IgM syndrome type 2
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 3.3 | GERP -3, phastCons 1 |
| Overall | ||
| CADD | 6.81 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.129%
African / African-American · 97/75,078 alleles
Filtering AF
0.108%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.101%
Overall
0.00774%
125/1,614,180 alleles · rare
exomes 67/1,461,820 · genomes 58/152,360 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.129% | 774 |
| Remaining individualsnot grpmax-eligible | 0.024% | 4,167 |
| Admixed American | 0.0117% | 8,573 |
| East Asian | 0.00891% | 11,221 |
| European (non-Finnish) | 0.000169% | 590,016 |
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.Arg127=
- Coding
- c.379C>A
- MANE Select
- NM_020661
- dbSNP
- rs141451637
- Type
- single nucleotide variant
- Location
- chr12:8605263 (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 127
- the cmp/dcmp-type deaminase domain; an α-helix
Similar variants
- AICDA p.Arg127Trp Uncertain significance ★ ⚠ same residue
- 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
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-arg127 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown