Is FLG p.Ser923fs (c.2767dup) pathogenic?

FLG p.Ser923fs (c.2767dup) is classified Pathogenic/Likely pathogenic in FLG (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-09-09). Rare (popmax 0.127%, sas); Associated with ichthyosis vulgaris.

What condition is associated with FLG p.Ser923fs (c.2767dup)?

FLG p.Ser923fs (c.2767dup) is associated with ichthyosis vulgaris (ClinVar).

How common is FLG p.Ser923fs (c.2767dup) in the general population?

FLG p.Ser923fs (c.2767dup) is rare (popmax 0.127%, sas) (gnomAD).

FLG p.Ser923fs

c.2767dup · rs748581094 · VCV2572530

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

rare (popmax 0.127%, sas)

Conditions

ichthyosis vulgaris

⚠ 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.
Consequence	frameshift	predicted loss-of-function; NMD-escape possible for C-terminal truncations
Splicing
SpliceAI	—	not looked up on this page · why
Overall
CADD	19.72	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 0.127% South Asian · 116/91,064 alleles

Filtering AF 0.108% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.101%

Overall 0.00731% 118/1,614,100 alleles · rare exomes 109/1,461,886 · genomes 9/152,214 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.127%	785
Remaining individualsnot grpmax-eligible	0.0032%	31,254

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.Ser923fs
Coding: c.2767dup
MANE Select: NM_002016
dbSNP: rs748581094
Type: Duplication
Location: chr1:152312118 (GRCh38)

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

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-ser923fs (accessed [today's date]).

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