Is AIDA p.Ile185Val (c.553A>G) pathogenic?

AIDA p.Ile185Val (c.553A>G) is classified Uncertain significance in AIDA (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-30). AlphaMissense: likely pathogenic (0.6222); Very rare (popmax 0.00336%, amr).

How common is AIDA p.Ile185Val (c.553A>G) in the general population?

AIDA p.Ile185Val (c.553A>G) is very rare (popmax 0.00336%, amr) (gnomAD).

What do computational predictors say about AIDA p.Ile185Val (c.553A>G)?

AlphaMissense predicts likely pathogenic (score 0.6222) — an in-silico prediction, not a clinical call.

AIDA p.Ile185Val

c.553A>G · rs1183488257 · VCV2314045

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6222 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00336%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6222	likely pathogenic
REVEL	0.209	benign-leaning
SaProt	LLR -6.57	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.1	GERP 2, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 42 kb · p 0.028 · regional, not allelic
Overall
CADD	23.7	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00336% Admixed American · 2/59,568 alleles

Filtering AF 0.000557% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000208%

Overall 0.000186% 3/1,611,662 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00336%	29,784
European (non-Finnish)	8.48e-05%	1,179,211

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: AIDA
Protein: p.Ile185Val
Coding: c.553A>G
MANE Select: NM_022831
dbSNP: rs1183488257
Type: single nucleotide variant
Location: chr1:222676126 (GRCh38)
Gene constraint: LOEUF 0.545 · pLI 0.93 (gnomAD)
Structure: AlphaFold pLDDT 86.37
Residue 185: the c2 aida-type domain; the 'axin-binding' region

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

Similar variants

AIDA p.Asn51Ser Uncertain significance ★ ⚠ same type
AIDA p.Asp134Tyr Uncertain significance ★ ⚠ same type
AIDA p.Asp186Asn Uncertain significance ★ ⚠ same type
AIDA p.Cys69Arg Uncertain significance ★ ⚠ same type
AIDA p.Glu265Val Uncertain significance ★ ⚠ same type
AIDA p.Glu45Lys Uncertain significance ★ ⚠ same type
AIDA p.Gly198Ser Uncertain significance ★ same type
AIDA p.Gly236Asp Uncertain significance ★ ⚠ same type

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/aida-p-ile185val (accessed [today's date]).

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