Is AICDA p.Val152= (c.456A>G) pathogenic?

AICDA p.Val152= (c.456A>G) is classified Likely benign in AICDA (ClinVar, Single submitter, 1 submitter; last evaluated 2026-01-11). Ultra-rare (popmax 0.0486%, amr); Associated with hyper-IgM syndrome type 2.

What condition is associated with AICDA p.Val152= (c.456A>G)?

AICDA p.Val152= (c.456A>G) is associated with hyper-IgM syndrome type 2 (ClinVar).

How common is AICDA p.Val152= (c.456A>G) in the general population?

AICDA p.Val152= (c.456A>G) is ultra-rare (popmax 0.0486%, amr) (gnomAD).

AICDA p.Val152=

c.456A>G · rs1263897145 · VCV1146427

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0486%, amr)

Conditions

hyper-IgM syndrome type 2

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.46	acceptor loss, 2 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP -0.16	GERP -3.4, phastCons 0.43
Overall
CADD	12.55	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0486% Admixed American · 27/55,528 alleles

Filtering AF 0.0343% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0295%

Overall 0.00177% 28/1,583,114 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0486%	2,057
African / African-American	0.0015%	66,886

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.Val152=
Coding: c.456A>G
MANE Select: NM_020661
dbSNP: rs1263897145
Type: single nucleotide variant
Location: chr12:8604894 (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.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
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-val152 (accessed [today's date]).

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