Is TDO2 p.Val306= (c.918G>A) pathogenic?

TDO2 p.Val306= (c.918G>A) is classified Benign/Likely benign in TDO2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-11-07). Rare (popmax 0.543%, nfe).

How common is TDO2 p.Val306= (c.918G>A) in the general population?

TDO2 p.Val306= (c.918G>A) is rare (popmax 0.543%, nfe) (gnomAD).

TDO2 p.Val306=

c.918G>A · rs144382797 · VCV716338

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.543%, nfe)

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 -0.43	GERP -4.3, phastCons 0.052
Overall
CADD	2.688	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.543% European (non-Finnish) · 6,404/1,178,570 alleles

Filtering AF 0.532% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.528%

Overall 0.47% 7,566/1,610,398 alleles · rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.943%	106
European (non-Finnish)grpmax	0.543%	184
Ashkenazi Jewishnot grpmax-eligible	0.536%	186
Remaining individualsnot grpmax-eligible	0.445%	225
Admixed American	0.11%	912
African / African-American	0.0669%	1,495
Middle Eastern	0.0166%	6,036
South Asian	0.00883%	11,319

Finnish 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: TDO2
Protein: p.Val306=
Coding: c.918G>A
MANE Select: NM_005651
dbSNP: rs144382797
Type: single nucleotide variant
Location: chr4:155917416 (GRCh38)
Gene constraint: LOEUF 1.104 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.63 · 22 PDB
Residue 306: an α-helix

Full TDO2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

TPH2 p.Pro206Ser Uncertain significance ★★ ⚠ same type
TPH2 c.-52A>G Benign ★★ same type
TPH2 c.*149G>A Likely benign ★★ same type
TPH2 c.*479G>A Benign ★★ same type
TPH2 p.Ala375= Benign ★★ same type
TPH2 p.Leu36Val Benign/Likely benign ★★ same type
TPH2 p.Pro180= Benign/Likely benign ★★ same type
TPH2 p.Pro312= Benign ★★ 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/tdo2-p-val306 (accessed [today's date]).

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