Is FAH p.Met1Val (c.1A>G) pathogenic?

FAH p.Met1Val (c.1A>G) is classified Pathogenic in FAH (ClinVar, Multiple submitters, 12 submitters; last evaluated 2026-01-11). Very rare (popmax 0.00167%, amr); Associated with tyrosinemia type I.

What condition is associated with FAH p.Met1Val (c.1A>G)?

FAH p.Met1Val (c.1A>G) is associated with tyrosinemia type I, tyrosinemia (ClinVar).

How common is FAH p.Met1Val (c.1A>G) in the general population?

FAH p.Met1Val (c.1A>G) is very rare (popmax 0.00167%, amr) (gnomAD).

How is Tyrosinemia type 1 inherited?

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

FAH p.Met1Val

c.1A>G · rs1057517972 · VCV372766

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 12 submitters

Consequence

start-loss

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Conditions

tyrosinemia type I

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	start-loss	predicted loss-of-function
REVEL	0.685	pathogenic-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.7, phastCons 1
Overall
CADD	23.2	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/60,028 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9e-05%

Overall 0.000479% 7/1,461,136 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	60,028
Remaining individualsnot grpmax-eligible	0.0016%	62,498
European (non-Finnish)	0.000424%	235,981

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.Met1Val
Coding: c.1A>G
MANE Select: NM_000137
dbSNP: rs1057517972
Type: single nucleotide variant
Location: chr15:80153055 (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

Also linked: tyrosinemia

For Tyrosinemia type 1 (Orphanet):

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

Similar variants

FAH p.Met1Ile Pathogenic ★★ same residue
FAH p.Met1Leu Likely pathogenic ★ same residue
FAH p.Met1Lys Likely pathogenic ★ same residue
FAH p.Met1_Ala7del Likely 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-met1val (accessed [today's date]).

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