Is AP1M2 p.Ile109= (c.327C>T) pathogenic?

AP1M2 p.Ile109= (c.327C>T) is classified Likely benign in AP1M2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-02). Ultra-rare (popmax 0.0164%, mid).

How common is AP1M2 p.Ile109= (c.327C>T) in the general population?

AP1M2 p.Ile109= (c.327C>T) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

AP1M2 p.Ile109=

c.327C>T · VCV4114612

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -6.1	GERP -3.7
Overall
CADD	5.864	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0164% Middle Eastern · 1/6,084 alleles

Filtering AF 0.000292% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000211%

Overall 0.000682% 11/1,613,846 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,084
East Asian	0.00223%	44,880
Remaining individualsnot grpmax-eligible	0.0016%	62,488
European (non-Finnish)	0.000678%	147,500

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: AP1M2
Protein: p.Ile109=
Coding: c.327C>T
MANE Select: NM_005498
Type: single nucleotide variant
Location: chr19:10581819 (GRCh38)
Gene constraint: LOEUF 1.073 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.03

Full AP1M2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

AP1M2 p.Ala156Gly Uncertain significance ★ ⚠ same type
AP1M2 p.Ala156Thr Uncertain significance ★ ⚠ same type
AP1M2 p.Ala3Val Uncertain significance ★ ⚠ same type
AP1M2 p.Ala405Thr Uncertain significance ★ ⚠ same type
AP1M2 p.Arg104Gln Uncertain significance ★ ⚠ same type
AP1M2 p.Arg148Gln Uncertain significance ★ ⚠ same type
AP1M2 p.Arg148Trp Uncertain significance ★ ⚠ same type
AP1M2 p.Arg19Cys 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/ap1m2-p-ile109 (accessed [today's date]).

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