Is FAH p.Asp233= (c.699C>T) pathogenic?

FAH p.Asp233= (c.699C>T) is classified Likely benign in FAH (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-11). Very rare (popmax 0.000425%, nfe); Associated with tyrosinemia type I.

What condition is associated with FAH p.Asp233= (c.699C>T)?

FAH p.Asp233= (c.699C>T) is associated with tyrosinemia type I (ClinVar).

How common is FAH p.Asp233= (c.699C>T) in the general population?

FAH p.Asp233= (c.699C>T) is very rare (popmax 0.000425%, nfe) (gnomAD).

How is Tyrosinemia type 1 inherited?

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

FAH p.Asp233=

c.699C>T · rs1358109972 · VCV1642273

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000425%, nfe)

Conditions

tyrosinemia type I

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 · C>G here scores Δ0.30 · evaluated, not missing
Constraint at this position
Conservation	phyloP 4	GERP 1.4, phastCons 1
Overall
CADD	11.79	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000425% European (non-Finnish) · 5/1,175,980 alleles

Filtering AF 0.000125% ClinGen BA1/BS1 input FAF95, joint · FAF99 9.1e-05%

Overall 0.000311% 5/1,609,582 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: FAH
Protein: p.Asp233=
Coding: c.699C>T
MANE Select: NM_000137
dbSNP: rs1358109972
Type: single nucleotide variant
Location: chr15:80172241 (GRCh38)
Gene constraint: LOEUF 1.067 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 98.06 · 8 PDB
Residue 233: a UniProt-annotated variant site (in tyrsn1; loss of activity); a binding site

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 p.Asp233Val Pathogenic/Likely pathogenic ★★ same residue
FAH p.Asp233Asn Conflicting classifications of pathogenicity ★ ⚠ same residue
FAH p.Asp233Glu Uncertain significance ⚠ same residue
FAH p.Asp233fs Pathogenic ★ same residue
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

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-asp233 (accessed [today's date]).

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