Is AP4M1 p.Asn185= (c.555T>C) pathogenic?

AP4M1 p.Asn185= (c.555T>C) is classified Likely benign in AP4M1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-09-19). Very rare (popmax 8.47e-05%, nfe); Associated with AP4M1-related disorder.

What condition is associated with AP4M1 p.Asn185= (c.555T>C)?

AP4M1 p.Asn185= (c.555T>C) is associated with AP4M1-related disorder (ClinVar).

How common is AP4M1 p.Asn185= (c.555T>C) in the general population?

AP4M1 p.Asn185= (c.555T>C) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

AP4M1 p.Asn185=

c.555T>C · rs1419965524 · VCV3053661

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Conditions

AP4M1-related disorder

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 -3.1	GERP -3.4
Overall
CADD	4.616	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,179,988 alleles

Overall 6.84e-05% 1/1,461,826 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: AP4M1
Protein: p.Asn185=
Coding: c.555T>C
MANE Select: NM_004722
dbSNP: rs1419965524
Type: single nucleotide variant
Location: chr7:100104103 (GRCh38)
Gene constraint: LOEUF 1.106 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.16 · 6 PDB
Residue 185: the mhd domain

Full AP4M1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

AP4M1-related disorder

Similar variants

AP4M1 c.1137+1G>T Pathogenic/Likely pathogenic ★★ same condition
AP4M1 p.Arg318Ter Pathogenic ★★ same condition
AP4M1 c.544-2A>T Likely pathogenic ★ same condition
AP4M1 p.Asn185fs Pathogenic ★ same residue
AP4M1 p.Arg441Ter Conflicting classifications of pathogenicity ★ same condition
AP4M1 p.Asp19= Uncertain significance ★ same condition
AP4M1 p.Gly371= Likely benign same condition
AP4M1 p.Leu347= Likely benign 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/ap4m1-p-asn185 (accessed [today's date]).

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