Is FECH p.Arg298Ter (c.892C>T) pathogenic?

FECH p.Arg298Ter (c.892C>T) is classified Pathogenic/Likely pathogenic in FECH (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-03-04). Very rare (popmax 0.00223%, eas); Associated with FECH-related disorders.

What condition is associated with FECH p.Arg298Ter (c.892C>T)?

FECH p.Arg298Ter (c.892C>T) is associated with FECH-related disorders (ClinVar).

How common is FECH p.Arg298Ter (c.892C>T) in the general population?

FECH p.Arg298Ter (c.892C>T) is very rare (popmax 0.00223%, eas) (gnomAD).

FECH p.Arg298Ter

c.892C>T · rs2050848238 · VCV1708448

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Conditions

FECH-related disorders

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 8 of 11
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4	GERP 0.79, phastCons 1
Overall
CADD	38.0	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 0.00223% East Asian · 1/44,868 alleles

Overall 0.000186% 3/1,614,092 alleles · very rare exomes 3/1,461,810 · genomes 0/152,282 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,868
South Asian	0.0011%	91,060
European (non-Finnish)	8.47e-05%	1,179,976

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.Arg298Ter
Coding: c.892C>T
MANE Select: NM_000140
dbSNP: rs2050848238
Type: single nucleotide variant
Location: chr18:57554865 (GRCh38)
Gene constraint: LOEUF 0.859 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.37 · 25 PDB
Residue 298: a β-strand

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

Disease context

FECH-related disorders

Similar variants

FECH c.314+2T>G Pathogenic/Likely pathogenic ★★ same condition
FECH c.599-2A>G Pathogenic ★★ same condition
FECH p.Arg96Ter Pathogenic/Likely pathogenic ★★ same condition
FECH p.Glu359= Pathogenic/Likely pathogenic ★★ same condition
FECH c.195-2A>T Pathogenic ★ same condition
FECH c.706-3C>G Likely pathogenic ★ same condition
FECH c.315-1G>C Likely pathogenic same condition
FECH p.Arg367Ter 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-arg298ter (accessed [today's date]).

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