Is FAH p.Asp290= (c.870C>T) pathogenic?

FAH p.Asp290= (c.870C>T) is classified Conflicting classifications of pathogenicity in FAH (ClinVar, Conflicting submitters, 6 submitters; last evaluated 2026-01-24). Rare (popmax 0.137%, amr); Associated with tyrosinemia type I.

What condition is associated with FAH p.Asp290= (c.870C>T)?

FAH p.Asp290= (c.870C>T) is associated with tyrosinemia type I (ClinVar).

How common is FAH p.Asp290= (c.870C>T) in the general population?

FAH p.Asp290= (c.870C>T) is rare (popmax 0.137%, amr) (gnomAD).

How is Tyrosinemia type 1 inherited?

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

FAH p.Asp290=

c.870C>T · rs377480457 · VCV385165

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

rare (popmax 0.137%, amr)

Conditions

tyrosinemia type I

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 0.031	GERP -0.88, phastCons 0.054
Overall
CADD	5.064	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.137% Admixed American · 82/59,998 alleles

Filtering AF 0.113% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.104%

Overall 0.0108% 174/1,613,938 alleles · rare exomes 160/1,461,854 · genomes 14/152,084 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.137%	732
East Asian	0.0201%	4,984
Middle Eastern	0.0164%	6,082
African / African-American	0.0134%	7,488
Remaining individualsnot grpmax-eligible	0.008%	12,498
European (non-Finnish)	0.00551%	18,154
South Asian	0.0022%	45,540

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: FAH
Protein: p.Asp290=
Coding: c.870C>T
MANE Select: NM_000137
dbSNP: rs377480457
Type: single nucleotide variant
Location: chr15:80175048 (GRCh38)
Gene constraint: LOEUF 1.067 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 98.06 · 8 PDB

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

Disease context

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

For Tyrosinemia type 1 (Orphanet):

Inheritance: Autosomal recessive
Onset: All ages
Prevalence: 1-9 / 1 000 000 (Worldwide)

Similar variants

FAH c.1062+5G>A Pathogenic/Likely pathogenic ★★ same condition
FAH c.1180+1G>A Pathogenic ★★ same condition
FAH c.192+1G>A Likely pathogenic ★★ same condition
FAH c.192+1G>T Pathogenic/Likely pathogenic ★★ same condition
FAH c.193-2A>G Likely pathogenic ★★ same condition
FAH c.314+1G>A Likely pathogenic ★★ same condition
FAH c.315-3C>G Pathogenic/Likely pathogenic ★★ same condition
FAH c.365-2A>G Likely 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/fah-p-asp290 (accessed [today's date]).

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