Is AICDA p.Ser43Thr (c.127T>A) pathogenic?

AICDA p.Ser43Thr (c.127T>A) is classified Uncertain significance in AICDA (ClinVar, Single submitter, 1 submitter; last evaluated 2020-08-10). AlphaMissense: likely benign (0.1822); Absent from gnomAD v4.1; Associated with hyper-IgM syndrome type 2.

What condition is associated with AICDA p.Ser43Thr (c.127T>A)?

AICDA p.Ser43Thr (c.127T>A) is associated with hyper-IgM syndrome type 2 (ClinVar).

How common is AICDA p.Ser43Thr (c.127T>A) in the general population?

AICDA p.Ser43Thr (c.127T>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about AICDA p.Ser43Thr (c.127T>A)?

AlphaMissense predicts likely benign (score 0.1822) — an in-silico prediction, not a clinical call.

AICDA p.Ser43Thr

c.127T>A · rs1941294885 · VCV998493

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1822 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

hyper-IgM syndrome type 2

Computational evidence

Protein change
AlphaMissense	0.1822	likely benign
REVEL	0.305	indeterminate
SaProt	LLR -4.29	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.9, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 8,480 bp · p 0.018 · regional, not allelic
Overall
CADD	20.4	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: AICDA
Protein: p.Ser43Thr
Coding: c.127T>A
MANE Select: NM_020661
dbSNP: rs1941294885
Type: single nucleotide variant
Location: chr12:8606894 (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 43: the cmp/dcmp-type deaminase domain; a β-strand

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.Ser43Leu 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-ser43thr (accessed [today's date]).

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