Is AP1G2 p.Asp437Asn (c.1309G>A) pathogenic?

AP1G2 p.Asp437Asn (c.1309G>A) is classified Uncertain significance in AP1G2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-10-06). AlphaMissense: likely benign (0.2494); Rare (popmax 0.149%, mid).

How common is AP1G2 p.Asp437Asn (c.1309G>A) in the general population?

AP1G2 p.Asp437Asn (c.1309G>A) is rare (popmax 0.149%, mid) (gnomAD).

What do computational predictors say about AP1G2 p.Asp437Asn (c.1309G>A)?

AlphaMissense predicts likely benign (score 0.2494) — an in-silico prediction, not a clinical call.

AP1G2 p.Asp437Asn

c.1309G>A · rs148842762 · VCV2407347

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2494 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.149%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2494	likely benign
REVEL	0.229	benign-leaning
SaProt	LLR -5.38	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 7.7	GERP 2.2, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 7,562 bp · p 0.22 · regional, not allelic
Overall
CADD	27.7	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 0.149% Middle Eastern · 9/6,056 alleles

Filtering AF 0.0775% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0579%

Overall 0.00477% 77/1,614,178 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.149%	673
African / African-American	0.0573%	1,746
Remaining individualsnot grpmax-eligible	0.0064%	15,627
Admixed American	0.005%	20,007
European (non-Finnish)	0.00144%	69,413
South Asian	0.0011%	91,066

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: AP1G2
Protein: p.Asp437Asn
Coding: c.1309G>A
MANE Select: NM_003917
dbSNP: rs148842762
Type: single nucleotide variant
Location: chr14:23563481 (GRCh38)
Gene constraint: LOEUF 1.004 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.13 · 4 PDB

Full AP1G2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

AP1G2 p.Ala181Pro Uncertain significance ★ ⚠ same type
AP1G2 p.Ala360Thr Uncertain significance ★ ⚠ same type
AP1G2 p.Ala430Val Uncertain significance ★ ⚠ same type
AP1G2 p.Ala465Glu Uncertain significance ★ ⚠ same type
AP1G2 p.Ala508Thr Uncertain significance ★ ⚠ same type
AP1G2 p.Ala527Val Uncertain significance ★ ⚠ same type
AP1G2 p.Ala76Thr Uncertain significance ★ ⚠ same type
AP1G2 p.Arg137Gln 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/ap1g2-p-asp437asn (accessed [today's date]).

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