Is IDO2 p.Leu238Phe (c.712C>T) pathogenic?

IDO2 p.Leu238Phe (c.712C>T) is classified Uncertain significance in IDO2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-25). AlphaMissense: likely benign (0.1621); Very rare (popmax 0.00861%, nfe).

How common is IDO2 p.Leu238Phe (c.712C>T) in the general population?

IDO2 p.Leu238Phe (c.712C>T) is very rare (popmax 0.00861%, nfe) (gnomAD).

What do computational predictors say about IDO2 p.Leu238Phe (c.712C>T)?

AlphaMissense predicts likely benign (score 0.1621) — an in-silico prediction, not a clinical call.

IDO2 p.Leu238Phe

c.712C>T · VCV4273470

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1621 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00861%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1621	likely benign
REVEL	0.349	indeterminate
SaProt	LLR -12.85	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 2.1, phastCons 1
Regional constraint	o/e 1.11	unconstrained · MANE · 66 kb · p 0.018 · regional, not allelic
Overall
CADD	22.6	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM L251F vs ClinVar L238F) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00861% European (non-Finnish) · 99/1,149,798 alleles

Filtering AF 0.00721% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00669%

Overall 0.00651% 102/1,567,656 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00861%	11,614
Remaining individualsnot grpmax-eligible	0.00497%	20,139

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.Leu238Phe
Coding: c.712C>T
MANE Select: NM_194294
Type: single nucleotide variant
Location: chr8:40005371 (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-leu238phe (accessed [today's date]).

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