Is FLG p.Arg612fs (c.1830del) pathogenic?

FLG p.Arg612fs (c.1830del) is classified Pathogenic in FLG (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-07). Absent from gnomAD; Associated with Inborn genetic diseases.

What condition is associated with FLG p.Arg612fs (c.1830del)?

FLG p.Arg612fs (c.1830del) is associated with Inborn genetic diseases, ichthyosis vulgaris (ClinVar).

How common is FLG p.Arg612fs (c.1830del) in the general population?

FLG p.Arg612fs (c.1830del) is absent from gnomAD (gnomAD).

FLG p.Arg612fs

c.1830del · rs1570913142 · VCV818057

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

Inborn genetic diseases

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 -2.2	GERP -2.5
Region caveats
Repeat context	tandem	chr1:152303355 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

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: FLG
Protein: p.Arg612fs
Coding: c.1830del
MANE Select: NM_023110 · reported on NM_002016
dbSNP: rs1570913142
Type: Deletion
Location: chr1:152313056 (GRCh38)
Structure: AlphaFold pLDDT 74.30 · 86 PDB
Residue 612: an α-helix; the protein kinase domain; a UniProt-annotated variant site (in hh2)

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: ichthyosis vulgaris

Similar variants

FLG p.Ser2279fs Pathogenic/Likely 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-arg612fs (accessed [today's date]).

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