Is AP4M1 p.Arg283Gln (c.848G>A) pathogenic?

AP4M1 p.Arg283Gln (c.848G>A) is classified Uncertain significance in AP4M1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-29). AlphaMissense: likely benign (0.0823); Ultra-rare (popmax 0.0329%, mid); Associated with Inborn genetic diseases.

What condition is associated with AP4M1 p.Arg283Gln (c.848G>A)?

AP4M1 p.Arg283Gln (c.848G>A) is associated with Inborn genetic diseases (ClinVar).

How common is AP4M1 p.Arg283Gln (c.848G>A) in the general population?

AP4M1 p.Arg283Gln (c.848G>A) is ultra-rare (popmax 0.0329%, mid) (gnomAD).

What do computational predictors say about AP4M1 p.Arg283Gln (c.848G>A)?

AlphaMissense predicts likely benign (score 0.0823) — an in-silico prediction, not a clinical call.

AP4M1 p.Arg283Gln

c.848G>A · VCV3301043

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0823 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0329%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0823	likely benign
REVEL	0.098	moderately benign-leaning
SaProt	LLR -8.27	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 2, phastCons 1
Regional constraint	o/e 1.07	unconstrained · MANE · 5,164 bp · p 0.093 · regional, not allelic
Overall
CADD	23.1	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 0.0329% Middle Eastern · 2/6,084 alleles

Filtering AF 0.0058% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00241%

Overall 0.00186% 30/1,613,932 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0329%	3,042
Remaining individualsnot grpmax-eligible	0.0032%	31,244
East Asian	0.00223%	44,892
South Asian	0.0022%	45,542
European (non-Finnish)	0.00186%	53,637
African / African-American	0.00134%	74,892

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.Arg283Gln
Coding: c.848G>A
MANE Select: NM_004722
Type: single nucleotide variant
Location: chr7:100105458 (GRCh38)
Gene constraint: LOEUF 1.106 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.16 · 6 PDB
Residue 283: the mhd domain; a β-strand

Full AP4M1 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

AP4M1 p.Arg283Trp Uncertain significance ★★ ⚠ same residue
AP4M1 p.Cys319Arg Pathogenic/Likely pathogenic ★★ same condition
AP4M1 c.673+6G>A Uncertain significance ★★ same condition
AP4M1 c.*449G>A Uncertain significance ★★ ⚠ same condition
AP4M1 p.Ala397Val Uncertain significance ★★ ⚠ same condition
AP4M1 p.Arg172His Uncertain significance ★★ ⚠ same condition
AP4M1 p.Arg271Cys Uncertain significance ★★ ⚠ same condition
AP4M1 p.Arg367Trp 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/ap4m1-p-arg283gln (accessed [today's date]).

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