Is FECH p.Gly16fs (c.47del) pathogenic?

FECH p.Gly16fs (c.47del) is classified Likely pathogenic in FECH (ClinVar, Single submitter, 1 submitter; last evaluated 2019-09-20). Very rare (popmax 0.00035%, nfe); Associated with autosomal erythropoietic protoporphyria.

What condition is associated with FECH p.Gly16fs (c.47del)?

FECH p.Gly16fs (c.47del) is associated with autosomal erythropoietic protoporphyria (ClinVar).

How common is FECH p.Gly16fs (c.47del) in the general population?

FECH p.Gly16fs (c.47del) is very rare (popmax 0.00035%, nfe) (gnomAD).

How is Autosomal erythropoietic protoporphyria inherited?

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

FECH p.Gly16fs

c.47del · rs2051380165 · VCV930105

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00035%, nfe)

Conditions

autosomal erythropoietic protoporphyria

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 1 of 11
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.61	GERP 0.37

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00035% European (non-Finnish) · 4/1,141,668 alleles

Filtering AF 8.2e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.5e-05%

Overall 0.000292% 4/1,369,688 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: FECH
Protein: p.Gly16fs
Coding: c.47del
MANE Select: NM_000140
dbSNP: rs2051380165
Type: Deletion
Location: chr18:57586574 (GRCh38)
Gene constraint: LOEUF 0.859 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.37 · 25 PDB

Full FECH gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

autosomal erythropoietic protoporphyria — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Autosomal erythropoietic protoporphyria (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive
Onset: Infancy, Neonatal
Prevalence: <1 / 1 000 000 (Europe)

Similar variants

FECH p.Gly16Asp Uncertain significance ★ ⚠ same residue
FECH c.315-48T>C Conflicting classifications of pathogenicity ★ same condition
FECH p.Glu351fs Pathogenic same condition
FECH p.Ala14fs Pathogenic ★★ same type
FECH p.Asp316fs Pathogenic/Likely pathogenic ★★ same type
FECH p.Lys379fs Pathogenic/Likely pathogenic ★★ same type
FECH p.Tyr194fs Pathogenic ★★ same type
FECH c.1077+1del Pathogenic ★ same type

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/fech-p-gly16fs (accessed [today's date]).

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