Is IDO2 p.Arg380= (c.1140G>A) pathogenic?

IDO2 p.Arg380= (c.1140G>A) is classified Likely benign in IDO2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-04-01). Very rare (popmax 0.00133%, afr).

How common is IDO2 p.Arg380= (c.1140G>A) in the general population?

IDO2 p.Arg380= (c.1140G>A) is very rare (popmax 0.00133%, afr) (gnomAD).

IDO2 p.Arg380=

c.1140G>A · rs1381206625 · VCV2658567

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.032	GERP -1.6, phastCons 0.021
Overall
CADD	6.047	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00133% African / African-American · 1/75,040 alleles

Filtering AF 0.000429% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000313%

Overall 0.000958% 14/1,461,686 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0048%	20,829
African / African-Americangrpmax	0.00133%	75,040
European (non-Finnish)	0.000848%	117,989

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: IDO2
Protein: p.Arg380=
Coding: c.1140G>A
MANE Select: NM_194294
dbSNP: rs1381206625
Type: single nucleotide variant
Location: chr8:40015518 (GRCh38)
Gene constraint: LOEUF 1.256 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.25 · 11 PDB
Residue 380: a UniProt-annotated variant site (loss of indoleamine 2,3-dioxygenase activity)

Full IDO2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

IDO2 p.Arg235Trp Benign ★★ same type
IDO2 p.Ile127Val Benign ★★ same type
IDO2 p.Tyr346Ter Benign ★★ same type
IDO2 p.Ala172Ser Uncertain significance ★ ⚠ same type
IDO2 p.Ala276Ser Uncertain significance ★ ⚠ same type
IDO2 p.Ala276Val Uncertain significance ★ ⚠ same type
IDO2 p.Ala339Thr Uncertain significance ★ ⚠ same type
IDO2 p.Ala341Gly 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/ido2-p-arg380 (accessed [today's date]).

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