Is FERMT1 p.Lys358= (c.1074A>G) pathogenic?

FERMT1 p.Lys358= (c.1074A>G) is classified Uncertain significance in FERMT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-12). Ultra-rare (popmax 0.0156%, eas); Associated with Kindler syndrome.

What condition is associated with FERMT1 p.Lys358= (c.1074A>G)?

FERMT1 p.Lys358= (c.1074A>G) is associated with Kindler syndrome (ClinVar).

How common is FERMT1 p.Lys358= (c.1074A>G) in the general population?

FERMT1 p.Lys358= (c.1074A>G) is ultra-rare (popmax 0.0156%, eas) (gnomAD).

How is Kindler epidermolysis bullosa inherited?

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

FERMT1 p.Lys358=

c.1074A>G · rs758819322 · VCV339219

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0156%, eas)

Conditions

Kindler syndrome

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 0.67	GERP -0.21, phastCons 0.79
Overall
CADD	5.937	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0156% East Asian · 7/44,828 alleles

Filtering AF 0.00727% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00515%

Overall 0.000434% 7/1,613,296 alleles · ultra-rare exomes 7/1,461,102 · genomes 0/152,194 · 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: FERMT1
Protein: p.Lys358=
Coding: c.1074A>G
MANE Select: NM_017671
dbSNP: rs758819322
Type: single nucleotide variant
Location: chr20:6096917 (GRCh38)
Gene constraint: LOEUF 0.871 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.14
Residue 358: the ferm domain

Full FERMT1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Kindler syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Kindler epidermolysis bullosa (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

FERMT1 c.1371+4A>G Pathogenic ★★ same condition
FERMT1 p.Arg110Ter Pathogenic ★★ same condition
FERMT1 p.Arg271Ter Pathogenic ★★ same condition
FERMT1 p.Arg288Ter Pathogenic ★★ same condition
FERMT1 p.Glu304Ter Pathogenic ★★ same condition
FERMT1 c.*1004G>A Uncertain significance ★★ same condition
FERMT1 c.*1076C>T Uncertain significance ★★ same condition
FERMT1 c.*2124C>A Uncertain significance ★★ 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/fermt1-p-lys358 (accessed [today's date]).

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