Is IDO2 p.Met1Arg (c.2T>G) pathogenic?

IDO2 p.Met1Arg (c.2T>G) is classified Uncertain significance in IDO2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-18). AlphaMissense: likely benign (0.0965); Very rare (popmax 0.00774%, nfe).

How common is IDO2 p.Met1Arg (c.2T>G) in the general population?

IDO2 p.Met1Arg (c.2T>G) is very rare (popmax 0.00774%, nfe) (gnomAD).

What do computational predictors say about IDO2 p.Met1Arg (c.2T>G)?

AlphaMissense predicts likely benign (score 0.0965) — an in-silico prediction, not a clinical call.

IDO2 p.Met1Arg

c.2T>G · VCV4273465

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0965 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00774%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Computational evidence

Protein change
AlphaMissense	0.0965	likely benign
Consequence	start-loss	predicted loss-of-function
REVEL	0.14	moderately benign-leaning
⇒ AlphaMissense and REVEL both call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.3	GERP 0.59, phastCons 1
Overall
CADD	22.5	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. Predicted loss-of-function is descriptive, not an applied PVS1 code.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM M14R vs ClinVar M1R) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00774% European (non-Finnish) · 91/1,176,076 alleles

Filtering AF 0.00641% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00594%

Overall 0.00616% 99/1,606,234 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00774%	12,924
Remaining individualsnot grpmax-eligible	0.00643%	15,560
Admixed American	0.00339%	29,477
African / African-American	0.00267%	37,417

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.Met1Arg
Coding: c.2T>G
MANE Select: NM_194294
Type: single nucleotide variant
Location: chr8:39949167 (GRCh38)
Gene constraint: LOEUF 1.256 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.25 · 11 PDB

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-met1arg (accessed [today's date]).

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