Is AICDA p.Pro123= (c.369C>T) pathogenic?

AICDA p.Pro123= (c.369C>T) is classified Benign/Likely benign in AICDA (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-20). Rare (popmax 0.556%, afr); Associated with hyper-IgM syndrome type 2.

What condition is associated with AICDA p.Pro123= (c.369C>T)?

AICDA p.Pro123= (c.369C>T) is associated with hyper-IgM syndrome type 2 (ClinVar).

How common is AICDA p.Pro123= (c.369C>T) in the general population?

AICDA p.Pro123= (c.369C>T) is rare (popmax 0.556%, afr) (gnomAD).

AICDA p.Pro123=

c.369C>T · rs199980715 · VCV779642

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.556%, afr)

Conditions

hyper-IgM syndrome type 2

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.095	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -3.9	GERP -3
Overall
CADD	3.855	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.556% African / African-American · 417/75,062 alleles

Filtering AF 0.511% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.494%

Overall 0.0405% 654/1,614,172 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.556%	180
Admixed American	0.05%	2,000
Remaining individualsnot grpmax-eligible	0.0432%	2,315
South Asian	0.0143%	7,007
European (non-Finnish)	0.0142%	7,066

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.Pro123=
Coding: c.369C>T
MANE Select: NM_020661
dbSNP: rs199980715
Type: single nucleotide variant
Location: chr12:8605273 (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 123: the cmp/dcmp-type deaminase domain; an α-helix

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

Disease context

hyper-IgM syndrome type 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

AICDA p.Pro123Leu 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-pro123 (accessed [today's date]).

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