Is AICDA p.Pro72Ala (c.214C>G) pathogenic?

AICDA p.Pro72Ala (c.214C>G) is classified Uncertain significance in AICDA (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-02). AlphaMissense: likely benign (0.1199); Very rare (popmax 0.00445%, eas); Associated with Inborn genetic diseases.

What condition is associated with AICDA p.Pro72Ala (c.214C>G)?

AICDA p.Pro72Ala (c.214C>G) is associated with Inborn genetic diseases (ClinVar).

How common is AICDA p.Pro72Ala (c.214C>G) in the general population?

AICDA p.Pro72Ala (c.214C>G) is very rare (popmax 0.00445%, eas) (gnomAD).

What do computational predictors say about AICDA p.Pro72Ala (c.214C>G)?

AlphaMissense predicts likely benign (score 0.1199) — an in-silico prediction, not a clinical call.

AICDA p.Pro72Ala

c.214C>G · VCV4028851

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1199 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00445%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1199	likely benign
REVEL	0.468	indeterminate
SaProt	LLR -7.50	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 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	26.4	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

Grpmax group 0.00445% East Asian · 2/44,894 alleles

Filtering AF 0.000738% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000276%

Overall 0.000137% 2/1,461,894 alleles · very rare

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.Pro72Ala
Coding: c.214C>G
MANE Select: NM_020661
Type: single nucleotide variant
Location: chr12:8605428 (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 72: 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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

AICDA p.Ala95Gly Uncertain significance ★★ ⚠ same condition
AICDA p.Ala95Val Uncertain significance ★★ ⚠ same condition
AICDA p.Arg50Cys Uncertain significance ★★ ⚠ same condition
AICDA p.Glu153Gln Uncertain significance ★★ ⚠ same condition
AICDA p.Phe97Leu Uncertain significance ★★ ⚠ same condition
AICDA p.Thr110Ile Uncertain significance ★★ ⚠ same condition
AICDA p.Arg128Leu Uncertain significance ★ ⚠ same condition
AICDA p.Leu5Met Uncertain significance ★ ⚠ 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-pro72ala (accessed [today's date]).

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