Is AP1M2 p.Arg104Gln (c.311G>A) pathogenic?

AP1M2 p.Arg104Gln (c.311G>A) is classified Uncertain significance in AP1M2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-09-01). AlphaMissense: ambiguous (0.3724); Rare (popmax 0.112%, nfe).

How common is AP1M2 p.Arg104Gln (c.311G>A) in the general population?

AP1M2 p.Arg104Gln (c.311G>A) is rare (popmax 0.112%, nfe) (gnomAD).

What do computational predictors say about AP1M2 p.Arg104Gln (c.311G>A)?

AlphaMissense predicts ambiguous (score 0.3724) — an in-silico prediction, not a clinical call.

AP1M2 p.Arg104Gln

c.311G>A · rs185906682 · VCV2221841

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3724 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.112%, nfe)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3724	ambiguous
REVEL	0.283	benign-leaning
SaProt	LLR -14.45	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.8	GERP 0.72, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 14 kb · p 0.022 · regional, not allelic
Overall
CADD	24.9	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 0.112% European (non-Finnish) · 1,322/1,179,934 alleles

Filtering AF 0.107% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.105%

Overall 0.0912% 1,472/1,613,764 alleles · rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.112%	893
Admixed American	0.1%	999
Remaining individualsnot grpmax-eligible	0.0992%	1,008
Middle Eastern	0.0825%	1,212
African / African-American	0.028%	3,569
East Asian	0.00223%	44,856
Finnishnot grpmax-eligible	0.00156%	63,978

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.Arg104Gln
Coding: c.311G>A
MANE Select: NM_005498
dbSNP: rs185906682
Type: single nucleotide variant
Location: chr19:10581835 (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.Arg148Gln Uncertain significance ★ ⚠ same type
AP1M2 p.Arg148Trp Uncertain significance ★ ⚠ same type
AP1M2 p.Arg19Cys Uncertain significance ★ ⚠ same type
AP1M2 p.Arg211Trp 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-arg104gln (accessed [today's date]).

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