Is FERMT1 p.Phe278= (c.834C>T) pathogenic?

FERMT1 p.Phe278= (c.834C>T) is classified Conflicting classifications of pathogenicity in FERMT1 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2022-11-24). Very rare (popmax 0.00334%, amr); Associated with Kindler syndrome.

What condition is associated with FERMT1 p.Phe278= (c.834C>T)?

FERMT1 p.Phe278= (c.834C>T) is associated with Kindler syndrome (ClinVar).

How common is FERMT1 p.Phe278= (c.834C>T) in the general population?

FERMT1 p.Phe278= (c.834C>T) is very rare (popmax 0.00334%, amr) (gnomAD).

How is Kindler epidermolysis bullosa inherited?

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

FERMT1 p.Phe278=

c.834C>T · rs775613961 · VCV339222

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00334%, amr)

Conditions

Kindler syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.31 · evaluated, not missing
Constraint at this position
Conservation	phyloP 1.5	GERP -4.4, phastCons 1
Overall
CADD	15.15	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00334% Admixed American · 2/59,928 alleles

Filtering AF 0.000554% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000212%

Overall 0.000684% 11/1,608,372 alleles · very rare exomes 10/1,456,262 · genomes 1/152,110 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00334%	29,964
African / African-American	0.00134%	74,794
European (non-Finnish)	0.000681%	146,939

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.Phe278=
Coding: c.834C>T
MANE Select: NM_017671
dbSNP: rs775613961
Type: single nucleotide variant
Location: chr20:6107547 (GRCh38)
Gene constraint: LOEUF 0.871 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.14
Residue 278: 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-phe278 (accessed [today's date]).

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