Is FAH p.Gln279= (c.837G>A) pathogenic?

FAH p.Gln279= (c.837G>A) is classified Uncertain significance in FAH (ClinVar, Single submitter, 2 submitters; last evaluated 2022-03-04). Very rare (popmax 6.19e-05%); Associated with tyrosinemia type I.

What condition is associated with FAH p.Gln279= (c.837G>A)?

FAH p.Gln279= (c.837G>A) is associated with tyrosinemia type I (ClinVar).

How common is FAH p.Gln279= (c.837G>A) in the general population?

FAH p.Gln279= (c.837G>A) is very rare (popmax 6.19e-05%) (gnomAD).

How is Tyrosinemia type 1 inherited?

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

FAH p.Gln279=

c.837G>A · rs375834291 · VCV2196396

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 6.19e-05%)

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 · G>T here scores Δ0.29 · evaluated, not missing
Pangolin	Δ0.43	loss · gain 0.01 · SpliceAI below 0.2 · independent
Constraint at this position
Conservation	phyloP 9.7	GERP 1.2, phastCons 1
Overall
CADD	16.01	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.19e-05%

Overall 6.19e-05% 1/1,614,210 alleles · very rare exomes 1/1,461,886 · genomes 0/152,324 · joint denominator

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.Gln279=
Coding: c.837G>A
MANE Select: NM_000137
dbSNP: rs375834291
Type: single nucleotide variant
Location: chr15:80173144 (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 279: a UniProt-annotated variant site (in tyrsn1; may affect splicing resulting in skipping of exon 8 alone or together with exon 9; lower activity as compared to wild type)

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.Gln279Arg Pathogenic/Likely pathogenic ★★ same residue
FAH p.Gln279Ter Likely pathogenic ★ same residue
FAH p.Gln279fs 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
FAH c.193-2A>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-gln279 (accessed [today's date]).

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