Is TPH2 p.Asp350= (c.1050T>C) pathogenic?

TPH2 p.Asp350= (c.1050T>C) is classified Uncertain significance in TPH2 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-13). Very rare (popmax 0.005%, amr); Associated with Tryptophan 5-monooxygenase deficiency.

What condition is associated with TPH2 p.Asp350= (c.1050T>C)?

TPH2 p.Asp350= (c.1050T>C) is associated with Tryptophan 5-monooxygenase deficiency (ClinVar).

How common is TPH2 p.Asp350= (c.1050T>C) in the general population?

TPH2 p.Asp350= (c.1050T>C) is very rare (popmax 0.005%, amr) (gnomAD).

TPH2 p.Asp350=

c.1050T>C · rs886049816 · VCV310387

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.005%, amr)

Conditions

Tryptophan 5-monooxygenase deficiency

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 -1.3	GERP -2.5, phastCons 0.001
Overall
CADD	5.976	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.005% Admixed American · 3/60,000 alleles

Filtering AF 0.00133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000668%

Overall 0.000434% 7/1,613,866 alleles · very rare exomes 6/1,461,642 · genomes 1/152,224 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.005%	20,000
Remaining individualsnot grpmax-eligible	0.0032%	31,239
African / African-American	0.00267%	37,464

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: TPH2
Protein: p.Asp350=
Coding: c.1050T>C
MANE Select: NM_173353
dbSNP: rs886049816
Type: single nucleotide variant
Location: chr12:71994547 (GRCh38)
Structure: AlphaFold pLDDT 90.63 · 22 PDB
Residue 350: an α-helix

Full TPH2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Tryptophan 5-monooxygenase deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

TPH2 c.-52A>G Benign ★★ same condition
TPH2 c.*149G>A Likely benign ★★ same condition
TPH2 c.*479G>A Benign ★★ same condition
TPH2 p.Ala375= Benign ★★ same condition
TPH2 p.Leu36Val Benign/Likely benign ★★ same condition
TPH2 p.Pro180= Benign/Likely benign ★★ same condition
TPH2 p.Pro312= Benign ★★ same condition
TPH2 c.1164+7A>G Uncertain significance ★ same condition

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/tph2-p-asp350 (accessed [today's date]).

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