Is AICDA p.Arg112Cys (c.334C>T) pathogenic?

AICDA p.Arg112Cys (c.334C>T) is classified Pathogenic in AICDA (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-07-03). AlphaMissense: likely pathogenic (0.8905); Very rare (popmax 0.00223%, eas); Associated with AICDA-related disorder.

What condition is associated with AICDA p.Arg112Cys (c.334C>T)?

AICDA p.Arg112Cys (c.334C>T) is associated with AICDA-related disorder, hyper-IgM syndrome type 2 (ClinVar).

How common is AICDA p.Arg112Cys (c.334C>T) in the general population?

AICDA p.Arg112Cys (c.334C>T) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about AICDA p.Arg112Cys (c.334C>T)?

AlphaMissense predicts likely pathogenic (score 0.8905) — an in-silico prediction, not a clinical call.

AICDA p.Arg112Cys

c.334C>T · rs1057520542 · VCV379250

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely pathogenic

0.8905 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

AICDA-related disorder

Computational evidence

Protein change
AlphaMissense	0.8905	likely pathogenic ✓ concordant with ClinVar
REVEL	0.695	pathogenic-leaning
SaProt	LLR -12.00	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.7, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 8,480 bp · p 0.018 · regional, not allelic
Overall
CADD	33.0	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

Grpmax group 0.00223% East Asian · 1/44,898 alleles

Filtering AF 0.000953% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000787%

Overall 0.0013% 21/1,614,146 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,898
Admixed American	0.00167%	60,012
Remaining individualsnot grpmax-eligible	0.0016%	62,488
European (non-Finnish)	0.00153%	65,558

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.Arg112Cys
Coding: c.334C>T
MANE Select: NM_020661
dbSNP: rs1057520542
Type: single nucleotide variant
Location: chr12:8605308 (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

Full AICDA gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

AICDA-related disorder

Also linked: hyper-IgM syndrome type 2

Similar variants

AICDA p.Arg112= Likely benign ★★ 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-arg112cys (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown