Is AICDA p.His155= (c.465C>T) pathogenic?

AICDA p.His155= (c.465C>T) is classified Benign/Likely benign in AICDA (ClinVar, Multiple submitters, 14 submitters; last evaluated 2026-02-04). Common (popmax 65.4%, amr) — too common for a highly-penetrant pathogenic allele; Associated with hyper-IgM syndrome type 2.

What condition is associated with AICDA p.His155= (c.465C>T)?

AICDA p.His155= (c.465C>T) is associated with hyper-IgM syndrome type 2 (ClinVar).

AICDA p.His155=

Q: How common is AICDA p.His155= (c.465C>T) in the general population?

AICDA p.His155= (c.465C>T) is common (popmax 65.4%, amr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.465C>T · rs2028373 · VCV261353

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 14 submitters

gnomAD v4.1

Common

common (popmax 65.4%, amr) — too common for a highly-penetrant pathogenic allele

Conditions

hyper-IgM syndrome type 2

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.02	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.1	GERP -3.4
Overall
CADD	3.025	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 65.4% Admixed American · 38,898/59,492 alleles

Filtering AF 64.8% ClinGen BA1/BS1 input FAF95, joint · FAF99 64.6%

Overall 61.8% 994,378/1,609,966 alleles · common

Ancestry group	Frequency	1 in
Admixed Americangrpmax	65.4%	2
Amishnot grpmax-eligible	64.9%	2
European (non-Finnish)	64.8%	2
Finnishnot grpmax-eligible	61.1%	2
Remaining individualsnot grpmax-eligible	60%	2
Ashkenazi Jewishnot grpmax-eligible	59.5%	2
South Asian	55.1%	2
Middle Eastern	55.1%	2
East Asian	47.1%	2
African / African-American	31.1%	3

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.His155=
Coding: c.465C>T
MANE Select: NM_020661
dbSNP: rs2028373
Type: single nucleotide variant
Location: chr12:8604885 (GRCh38)
Gene constraint: LOEUF 1.144 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 88.43 · 5 PDB

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.His155Gln Uncertain significance ★ ⚠ same residue
AICDA p.His155Arg 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

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-his155 (accessed [today's date]).

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