Is AP1G2 p.Arg736Gln (c.2207G>A) pathogenic?

AP1G2 p.Arg736Gln (c.2207G>A) is classified Likely benign in AP1G2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-10-18). AlphaMissense: likely benign (0.0599); Rare (popmax 0.805%, mid).

How common is AP1G2 p.Arg736Gln (c.2207G>A) in the general population?

AP1G2 p.Arg736Gln (c.2207G>A) is rare (popmax 0.805%, mid) (gnomAD).

What do computational predictors say about AP1G2 p.Arg736Gln (c.2207G>A)?

AlphaMissense predicts likely benign (score 0.0599) — an in-silico prediction, not a clinical call.

AP1G2 p.Arg736Gln

c.2207G>A · rs201878577 · VCV2346035

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0599 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.805%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0599	likely benign
REVEL	0.008	strongly benign-leaning
SaProt	LLR -6.33	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 -0.33	GERP -4.4
Regional constraint	o/e 0.96	unconstrained · MANE · 7,562 bp · p 0.22 · regional, not allelic
Overall
CADD	20.5	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 0.805% Middle Eastern · 48/5,966 alleles

Filtering AF 0.623% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.559%

Overall 0.0299% 483/1,613,004 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.805%	124
Ashkenazi Jewishnot grpmax-eligible	0.395%	253
Admixed American	0.0918%	1,090
Remaining individualsnot grpmax-eligible	0.0673%	1,486
European (non-Finnish)	0.0171%	5,839
African / African-American	0.012%	8,333
South Asian	0.0066%	15,152
Finnishnot grpmax-eligible	0.0047%	21,289
East Asian	0.00223%	44,876

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.Arg736Gln
Coding: c.2207G>A
MANE Select: NM_003917
dbSNP: rs201878577
Type: single nucleotide variant
Location: chr14:23559987 (GRCh38)
Gene constraint: LOEUF 1.004 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.13 · 4 PDB
Residue 736: the gae domain; a turn

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

Similar variants

AP1G2 p.Arg736Trp Uncertain significance ★ ⚠ same residue
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

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-arg736gln (accessed [today's date]).

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