Is FERMT1 p.Phe565= (c.1695T>C) pathogenic?

FERMT1 p.Phe565= (c.1695T>C) is classified Benign in FERMT1 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-02-04). Common (popmax 63.4%, eas) — too common for a highly-penetrant pathogenic allele; Associated with Kindler syndrome.

What condition is associated with FERMT1 p.Phe565= (c.1695T>C)?

FERMT1 p.Phe565= (c.1695T>C) is associated with Kindler syndrome (ClinVar).

How is Kindler epidermolysis bullosa inherited?

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

FERMT1 p.Phe565=

Q: How common is FERMT1 p.Phe565= (c.1695T>C) in the general population?

FERMT1 p.Phe565= (c.1695T>C) is common (popmax 63.4%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1695T>C · rs753927 · VCV260868

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Common

common (popmax 63.4%, eas) — too common for a highly-penetrant pathogenic allele

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 -3.7	GERP -4.3
Overall
CADD	1.248	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 63.4% East Asian · 28,414/44,826 alleles

Filtering AF 62.8% ClinGen BA1/BS1 input FAF95, joint · FAF99 62.5%

Overall 36.4% 586,978/1,612,042 alleles · common exomes 530,625/1,459,886 · genomes 56,353/152,156 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	63.4%	2
Admixed American	47.5%	2
Amishnot grpmax-eligible	41.6%	2
Middle Eastern	37.3%	3
Ashkenazi Jewishnot grpmax-eligible	37.3%	3
Remaining individualsnot grpmax-eligible	37.2%	3
European (non-Finnish)	36%	3
African / African-American	34.8%	3
South Asian	27.5%	4
Finnishnot grpmax-eligible	27.3%	4

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.Phe565=
Coding: c.1695T>C
MANE Select: NM_017671
dbSNP: rs753927
Type: single nucleotide variant
Location: chr20:6084063 (GRCh38)
Gene constraint: LOEUF 0.871 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.14
Residue 565: 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-phe565 (accessed [today's date]).

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