Is FAH p.Lys47= (c.141G>A) pathogenic?

FAH p.Lys47= (c.141G>A) is classified Conflicting classifications of pathogenicity in FAH (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2023-11-09). Very rare (popmax 0.00133%, afr); Associated with tyrosinemia type I.

What condition is associated with FAH p.Lys47= (c.141G>A)?

FAH p.Lys47= (c.141G>A) is associated with tyrosinemia type I (ClinVar).

How common is FAH p.Lys47= (c.141G>A) in the general population?

FAH p.Lys47= (c.141G>A) is very rare (popmax 0.00133%, afr) (gnomAD).

How is Tyrosinemia type 1 inherited?

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

FAH p.Lys47=

c.141G>A · rs1202678414 · VCV501161

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

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 0.73	GERP -2.9, phastCons 1
Overall
CADD	1.915	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00133% African / African-American · 1/74,920 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000248% 4/1,614,050 alleles · very rare exomes 3/1,461,868 · genomes 1/152,182 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0016%	62,490
African / African-Americangrpmax	0.00133%	74,920
European (non-Finnish)	0.000169%	590,009

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Lys47=
Coding: c.141G>A
MANE Select: NM_000137
dbSNP: rs1202678414
Type: single nucleotide variant
Location: chr15:80158119 (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.Lys47Glu Benign ★★ ⚠ 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
FAH c.315-3C>G 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-lys47 (accessed [today's date]).

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