Is TAT p.Asp19= (c.57C>T) pathogenic?

TAT p.Asp19= (c.57C>T) is classified Likely benign in TAT (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-02-01). Ultra-rare (popmax 0.0164%, mid); Associated with tyrosinemia type II.

What condition is associated with TAT p.Asp19= (c.57C>T)?

TAT p.Asp19= (c.57C>T) is associated with tyrosinemia type II (ClinVar).

How common is TAT p.Asp19= (c.57C>T) in the general population?

TAT p.Asp19= (c.57C>T) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

How is Tyrosinemia type 2 inherited?

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

TAT p.Asp19=

c.57C>T · rs777582600 · VCV1083807

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

Conditions

tyrosinemia type II

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 -1.4	GERP -3.5
Overall
CADD	3.43	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0164% Middle Eastern · 1/6,082 alleles

Filtering AF 0.00662% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00483%

Overall 0.00173% 28/1,613,978 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,082
Admixed American	0.0133%	7,498
Remaining individualsnot grpmax-eligible	0.0016%	62,482
European (non-Finnish)	0.00153%	65,557

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.Asp19=
Coding: c.57C>T
MANE Select: NM_000353
dbSNP: rs777582600
Type: single nucleotide variant
Location: chr16:71576359 (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 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
TAT p.Arg57Ter 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-asp19 (accessed [today's date]).

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