Is FERMT1 p.Ser472= (c.1416G>A) pathogenic?

FERMT1 p.Ser472= (c.1416G>A) is classified Benign in FERMT1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-25). Low-frequency (popmax 1.95%, afr); Associated with Kindler syndrome.

What condition is associated with FERMT1 p.Ser472= (c.1416G>A)?

FERMT1 p.Ser472= (c.1416G>A) is associated with Kindler syndrome (ClinVar).

How common is FERMT1 p.Ser472= (c.1416G>A) in the general population?

FERMT1 p.Ser472= (c.1416G>A) is low-frequency (popmax 1.95%, afr) (gnomAD).

How is Kindler epidermolysis bullosa inherited?

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

FERMT1 p.Ser472=

c.1416G>A · rs148992845 · VCV339215

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.95%, afr)

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 -14	GERP -3.7
Overall
CADD	0.323	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.95% African / African-American · 1,463/75,012 alleles

Filtering AF 1.87% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.83%

Overall 0.106% 1,716/1,614,050 alleles · low-frequency exomes 871/1,461,810 · genomes 845/152,240 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.95%	51
Remaining individualsnot grpmax-eligible	0.0864%	1,157
Middle Eastern	0.0833%	1,200
Admixed American	0.0733%	1,364
South Asian	0.0439%	2,277
European (non-Finnish)	0.00924%	10,826
East Asian	0.00223%	44,878

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.Ser472=
Coding: c.1416G>A
MANE Select: NM_017671
dbSNP: rs148992845
Type: single nucleotide variant
Location: chr20:6085243 (GRCh38)
Gene constraint: LOEUF 0.871 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.14
Residue 472: the ferm domain; the ph 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 p.Ser472Leu Uncertain significance ★★ ⚠ same residue
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

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-ser472 (accessed [today's date]).

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