Is FLG p.Ser609fs (c.1826del) pathogenic?

FLG p.Ser609fs (c.1826del) is classified Pathogenic in FLG (ClinVar, Single submitter, 1 submitter; last evaluated 2026-04-09). Ultra-rare (popmax 0.0253%, sas).

How common is FLG p.Ser609fs (c.1826del) in the general population?

FLG p.Ser609fs (c.1826del) is ultra-rare (popmax 0.0253%, sas) (gnomAD).

FLG p.Ser609fs

c.1826del · VCV3602925

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0253%, sas)

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function; NMD-escape possible for C-terminal truncations
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -14	GERP -2.5
Overall
CADD	12.94	PHRED · no single calibrated threshold — expert panels disagree
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

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0253% South Asian · 23/91,072 alleles

Filtering AF 0.0172% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0146%

Overall 0.00155% 25/1,613,748 alleles · ultra-rare exomes 20/1,461,884 · genomes 5/151,864 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0253%	3,960
Remaining individualsnot grpmax-eligible	0.0032%	31,239

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.Ser609fs
Coding: c.1826del
MANE Select: NM_002016
Type: Deletion
Location: chr1:152313060 (GRCh38)

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

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-ser609fs (accessed [today's date]).

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