Is FECH p.Gln122fs (c.365del) pathogenic?

FECH p.Gln122fs (c.365del) is classified Likely pathogenic in FECH (ClinVar, Single submitter, 1 submitter; last evaluated 2019-05-28). Absent from gnomAD; Associated with protoporphyria, erythropoietic, 1.

What condition is associated with FECH p.Gln122fs (c.365del)?

FECH p.Gln122fs (c.365del) is associated with protoporphyria, erythropoietic, 1 (ClinVar).

How common is FECH p.Gln122fs (c.365del) in the general population?

FECH p.Gln122fs (c.365del) is absent from gnomAD (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.Gln122fs

c.365del · rs1599003455 · VCV803501

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

protoporphyria, erythropoietic, 1

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 4 of 11
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.4	GERP -2.6, phastCons 1

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: FECH
Protein: p.Gln122fs
Coding: c.365del
MANE Select: NM_000140
dbSNP: rs1599003455
Type: Deletion
Location: chr18:57571490 (GRCh38)
Gene constraint: LOEUF 0.859 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.37 · 25 PDB
Residue 122: an α-helix

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

Disease context

protoporphyria, erythropoietic, 1 — 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.Ala14fs Pathogenic ★★ same condition
FECH p.Lys379fs Pathogenic/Likely pathogenic ★★ same condition
FECH p.Tyr194fs Pathogenic ★★ same condition
FECH p.Ile134fs Pathogenic ★ same condition
FECH c.1137+3A>G Pathogenic/Likely pathogenic ★★ same condition
FECH c.314+2T>G Pathogenic/Likely pathogenic ★★ same condition
FECH c.463+1G>C Pathogenic ★★ same condition
FECH c.598+1G>T 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/fech-p-gln122fs (accessed [today's date]).

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