Is AP1G2 p.Arg155His (c.464G>A) pathogenic?

AP1G2 p.Arg155His (c.464G>A) is classified Likely pathogenic in AP1G2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-07-01). AlphaMissense: likely benign (0.1994); Ultra-rare (popmax 0.0167%, amr); Associated with esophageal atresia/tracheoesophageal fistula.

What condition is associated with AP1G2 p.Arg155His (c.464G>A)?

AP1G2 p.Arg155His (c.464G>A) is associated with esophageal atresia/tracheoesophageal fistula (ClinVar).

How common is AP1G2 p.Arg155His (c.464G>A) in the general population?

AP1G2 p.Arg155His (c.464G>A) is ultra-rare (popmax 0.0167%, amr) (gnomAD).

What do computational predictors say about AP1G2 p.Arg155His (c.464G>A)?

AlphaMissense predicts likely benign (score 0.1994) — an in-silico prediction, not a clinical call.

AP1G2 p.Arg155His

c.464G>A · rs200202756 · VCV916555

Likely pathogenic No assertion criteria

Classification

Likely pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1994 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0167%, amr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

esophageal atresia/tracheoesophageal fistula

Computational evidence

Protein change
AlphaMissense	0.1994	likely benign ⚠ discordant with ClinVar
REVEL	0.388	indeterminate
SaProt	LLR -10.76	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.7	GERP 1.3, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 7,562 bp · p 0.22 · regional, not allelic
Overall
CADD	26.5	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 0.0167% Admixed American · 10/59,974 alleles

Filtering AF 0.009% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00682%

Overall 0.00539% 87/1,613,594 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0167%	5,997
European (non-Finnish)	0.00619%	16,163
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,586
East Asian	0.00223%	44,886
Remaining individualsnot grpmax-eligible	0.0016%	62,470
African / African-American	0.00133%	74,910

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.Arg155His
Coding: c.464G>A
MANE Select: NM_003917
dbSNP: rs200202756
Type: single nucleotide variant
Location: chr14:23566285 (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

Disease context

esophageal atresia/tracheoesophageal fistula — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

AP1G2 p.Arg155Cys 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-arg155his (accessed [today's date]).

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