Is FLG p.Ser2279fs (c.6834_6838del) pathogenic?

FLG p.Ser2279fs (c.68346838del) is classified Pathogenic/Likely pathogenic in FLG (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-05-06). Ultra-rare (popmax 0.0267%, eas); Associated with ichthyosis vulgaris.

What condition is associated with FLG p.Ser2279fs (c.6834_6838del)?

FLG p.Ser2279fs (c.6834_6838del) is associated with ichthyosis vulgaris, dermatitis, atopic, 2 (ClinVar).

How common is FLG p.Ser2279fs (c.6834_6838del) in the general population?

FLG p.Ser2279fs (c.6834_6838del) is ultra-rare (popmax 0.0267%, eas) (gnomAD).

FLG p.Ser2279fs

c.6834_6838del · rs772007167 · VCV1723739

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0267%, eas)

Conditions

ichthyosis vulgaris

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen); NMD-escape possible for C-terminal truncations
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -1.6	GERP 0.59
Overall
CADD	23.7	PHRED · no single calibrated threshold — expert panels disagree
Region caveats
Repeat context	tandem	chr1:152308215 segmental duplication, simple repeat · ambiguous alignment · reads may not map uniquely · confidence, not pathogenicity

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0267% East Asian · 12/44,892 alleles

Filtering AF 0.0154% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0121%

Overall 0.000867% 14/1,614,034 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0267%	3,741
Remaining individualsnot grpmax-eligible	0.0032%	31,243

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: FLG
Protein: p.Ser2279fs
Coding: c.6834_6838del
MANE Select: NM_023110 · reported on NM_002016
dbSNP: rs772007167
Type: Deletion
Location: chr1:152308048 (GRCh38)
Structure: AlphaFold pLDDT 74.30 · 86 PDB

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

Disease context

ichthyosis vulgaris — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: dermatitis, atopic, 2

Similar variants

FLG p.Arg612fs Pathogenic ★★ same condition
FLG p.Arg1684fs Likely pathogenic ★ same condition
FLG p.Gln2962fs Likely pathogenic ★ same condition
FLG p.Gln776fs Likely pathogenic ★ same condition
FLG p.Gly2876fs Likely pathogenic ★ same condition
FLG p.Gly3683fs Likely pathogenic ★ same condition
FLG p.Ile3642fs Likely pathogenic ★ same condition
FLG p.Ser1013fs Likely pathogenic ★ 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/flg-p-ser2279fs (accessed [today's date]).

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