Is FAH p.Pro30= (c.90G>A) pathogenic?

FAH p.Pro30= (c.90G>A) is classified Likely benign in FAH (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-23). Rare (popmax 0.118%, eas); Associated with tyrosinemia type I.

What condition is associated with FAH p.Pro30= (c.90G>A)?

FAH p.Pro30= (c.90G>A) is associated with tyrosinemia type I (ClinVar).

How common is FAH p.Pro30= (c.90G>A) in the general population?

FAH p.Pro30= (c.90G>A) is rare (popmax 0.118%, eas) (gnomAD).

How is Tyrosinemia type 1 inherited?

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

FAH p.Pro30=

c.90G>A · rs202195651 · VCV1119061

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

rare (popmax 0.118%, eas)

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 -5.7	GERP -2.9
Overall
CADD	0.281	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.118% East Asian · 53/44,858 alleles

Filtering AF 0.0927% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0836%

Overall 0.0122% 197/1,613,300 alleles · rare exomes 167/1,461,062 · genomes 30/152,238 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.118%	846
Finnishnot grpmax-eligible	0.114%	877
Remaining individualsnot grpmax-eligible	0.0128%	7,810
South Asian	0.00769%	13,008
European (non-Finnish)	0.00449%	22,251
African / African-American	0.004%	25,007

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.Pro30=
Coding: c.90G>A
MANE Select: NM_000137
dbSNP: rs202195651
Type: single nucleotide variant
Location: chr15:80158068 (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 p.Pro30Leu Uncertain significance ★ ⚠ same residue
FAH p.Pro30Gln Uncertain significance ⚠ 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
FAH c.193-2A>G Likely pathogenic ★★ same condition
FAH c.314+1G>A 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-pro30 (accessed [today's date]).

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