Is TAT p.Ser28= (c.84C>T) pathogenic?

TAT p.Ser28= (c.84C>T) is classified Likely benign in TAT (ClinVar, Single submitter, 1 submitter; last evaluated 2026-01-21). Very rare (popmax 0.00891%, eas); Associated with tyrosinemia type II.

What condition is associated with TAT p.Ser28= (c.84C>T)?

TAT p.Ser28= (c.84C>T) is associated with tyrosinemia type II (ClinVar).

How common is TAT p.Ser28= (c.84C>T) in the general population?

TAT p.Ser28= (c.84C>T) is very rare (popmax 0.00891%, eas) (gnomAD).

How is Tyrosinemia type 2 inherited?

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

TAT p.Ser28=

c.84C>T · rs184872582 · VCV1092428

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00891%, eas)

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 5	GERP -0.002, phastCons 1
Overall
CADD	10.05	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00891% East Asian · 4/44,884 alleles

Filtering AF 0.00298% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0018%

Overall 0.000434% 7/1,614,188 alleles · very rare exomes 6/1,461,892 · genomes 1/152,296 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00891%	11,221
South Asian	0.0022%	45,539
Remaining individualsnot grpmax-eligible	0.0016%	62,512

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.Ser28=
Coding: c.84C>T
MANE Select: NM_000353
dbSNP: rs184872582
Type: single nucleotide variant
Location: chr16:71576332 (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-ser28 (accessed [today's date]).

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