Is FERMT1 p.Ser338= (c.1014C>T) pathogenic?

FERMT1 p.Ser338= (c.1014C>T) is classified Conflicting classifications of pathogenicity in FERMT1 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2026-01-15). Rare (popmax 0.312%, nfe); Associated with Kindler syndrome.

What condition is associated with FERMT1 p.Ser338= (c.1014C>T)?

FERMT1 p.Ser338= (c.1014C>T) is associated with Kindler syndrome (ClinVar).

How common is FERMT1 p.Ser338= (c.1014C>T) in the general population?

FERMT1 p.Ser338= (c.1014C>T) is rare (popmax 0.312%, nfe) (gnomAD).

How is Kindler epidermolysis bullosa inherited?

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

FERMT1 p.Ser338=

c.1014C>T · rs138986656 · VCV339221

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

rare (popmax 0.312%, nfe)

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 -0.094	GERP -4.1, phastCons 0.006
Overall
CADD	4.206	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.312% European (non-Finnish) · 3,684/1,179,898 alleles

Filtering AF 0.304% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.3%

Overall 0.267% 4,305/1,613,772 alleles · rare exomes 4,062/1,461,724 · genomes 243/152,048 · joint denominator

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	1.86%	54
European (non-Finnish)grpmax	0.312%	320
South Asian	0.306%	326
Remaining individualsnot grpmax-eligible	0.25%	401
Finnishnot grpmax-eligible	0.128%	780
Admixed American	0.0984%	1,017
Middle Eastern	0.0825%	1,212
African / African-American	0.0267%	3,747
Ashkenazi Jewishnot grpmax-eligible	0.00676%	14,798
East Asian	0.00223%	44,870

Amish 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: FERMT1
Protein: p.Ser338=
Coding: c.1014C>T
MANE Select: NM_017671
dbSNP: rs138986656
Type: single nucleotide variant
Location: chr20:6096977 (GRCh38)
Gene constraint: LOEUF 0.871 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.14
Residue 338: 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-ser338 (accessed [today's date]).

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