Is TAT p.Pro69= (c.207A>G) pathogenic?

TAT p.Pro69= (c.207A>G) is classified Likely benign in TAT (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-30). Very rare (popmax 0.000424%, nfe); Associated with tyrosinemia type II.

What condition is associated with TAT p.Pro69= (c.207A>G)?

TAT p.Pro69= (c.207A>G) is associated with tyrosinemia type II (ClinVar).

How common is TAT p.Pro69= (c.207A>G) in the general population?

TAT p.Pro69= (c.207A>G) is very rare (popmax 0.000424%, nfe) (gnomAD).

How is Tyrosinemia type 2 inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

TAT p.Pro69=

c.207A>G · rs1383405389 · VCV1112520

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000424%, nfe)

Conditions

tyrosinemia type II

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>A here scores Δ0.20 · evaluated, not missing
Constraint at this position
Conservation	phyloP -1.7	GERP -3.8
Overall
CADD	7.889	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000424% European (non-Finnish) · 5/1,180,024 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9e-05%

Overall 0.000342% 5/1,461,848 alleles · very rare

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: TAT
Protein: p.Pro69=
Coding: c.207A>G
MANE Select: NM_000353
dbSNP: rs1383405389
Type: single nucleotide variant
Location: chr16:71576209 (GRCh38)
Gene constraint: LOEUF 0.844 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.93 · 1 PDB

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

Disease context

tyrosinemia type II — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Tyrosinemia type 2 (Orphanet):

Inheritance: Autosomal recessive
Onset: Adolescent, Childhood, Infancy, Neonatal

Similar variants

TAT p.Pro69Ser Uncertain significance ★ ⚠ same residue
TAT c.707-2A>G Pathogenic/Likely pathogenic ★★ same condition
TAT c.912+1G>A Likely pathogenic ★★ same condition
TAT p.Arg119Trp Pathogenic/Likely pathogenic ★★ same condition
TAT p.Arg297Ter Pathogenic/Likely pathogenic ★★ same condition
TAT p.Arg306Ter Pathogenic/Likely pathogenic ★★ same condition
TAT p.Arg417Gln Pathogenic/Likely pathogenic ★★ same condition
TAT p.Arg417Ter Pathogenic ★★ 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/tat-p-pro69 (accessed [today's date]).

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