Is IDO2 p.Ala172Ser (c.514G>T) pathogenic?

IDO2 p.Ala172Ser (c.514G>T) is classified Uncertain significance in IDO2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-27). AlphaMissense: likely benign (0.1333); Very rare (popmax 0.00167%, amr).

How common is IDO2 p.Ala172Ser (c.514G>T) in the general population?

IDO2 p.Ala172Ser (c.514G>T) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about IDO2 p.Ala172Ser (c.514G>T)?

AlphaMissense predicts likely benign (score 0.1333) — an in-silico prediction, not a clinical call.

IDO2 p.Ala172Ser

c.514G>T · rs749382557 · VCV2402150

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1333 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Computational evidence

Protein change
AlphaMissense	0.1333	likely benign
REVEL	0.081	moderately benign-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this tolerated; SaProt makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.6	GERP -0.18, phastCons 1
Regional constraint	o/e 1.11	unconstrained · MANE · 66 kb · p 0.018 · regional, not allelic
Overall
CADD	17.72	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 is an independent agreement signal.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM A185S vs ClinVar A172S) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/59,730 alleles

Filtering AF 0.000879% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000718%

Overall 0.00689% 111/1,610,998 alleles · very rare exomes 102/1,458,834 · genomes 9/152,164 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.275%	364
Remaining individualsnot grpmax-eligible	0.0192%	5,199
Admixed Americangrpmax	0.00167%	59,730
European (non-Finnish)	0.00144%	69,320

Ashkenazi Jewish 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.Ala172Ser
Coding: c.514G>T
MANE Select: NM_194294
dbSNP: rs749382557
Type: single nucleotide variant
Location: chr8:39987935 (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.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
IDO2 p.Ala61Pro 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-ala172ser (accessed [today's date]).

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