Is FLG p.Ser3398= (c.10194T>C) pathogenic?

FLG p.Ser3398= (c.10194T>C) is classified Benign in FLG (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-11). Common (popmax 62%, eas) — too common for a highly-penetrant pathogenic allele; Associated with ichthyosis vulgaris.

What condition is associated with FLG p.Ser3398= (c.10194T>C)?

FLG p.Ser3398= (c.10194T>C) is associated with ichthyosis vulgaris (ClinVar).

FLG p.Ser3398=

Q: How common is FLG p.Ser3398= (c.10194T>C) in the general population?

FLG p.Ser3398= (c.10194T>C) is common (popmax 62%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.10194T>C · rs3091276 · VCV2585646

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Common

common (popmax 62%, eas) — too common for a highly-penetrant pathogenic allele

Conditions

ichthyosis vulgaris

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 -7.7	GERP -3.5
Overall
CADD	0.135	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 62% East Asian · 26,756/43,180 alleles

Filtering AF 61.3% ClinGen BA1/BS1 input FAF95, joint · FAF99 61.1%

Overall 21% 327,513/1,561,328 alleles · common exomes 282,844/1,413,850 · genomes 44,669/147,478 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	62%	2
African / African-American	51.4%	2
Admixed American	43.7%	2
South Asian	40.5%	2
Ashkenazi Jewishnot grpmax-eligible	30.1%	3
Middle Eastern	29.2%	3
Remaining individualsnot grpmax-eligible	25.6%	4
Finnishnot grpmax-eligible	17.3%	6
Amishnot grpmax-eligible	16.9%	6
European (non-Finnish)	14.5%	7

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.Ser3398=
Coding: c.10194T>C
MANE Select: NM_002016
dbSNP: rs3091276
Type: single nucleotide variant
Location: chr1:152304692 (GRCh38)
Gene constraint: LOEUF 1.932 · pLI <0.01 (gnomAD)
Residue 3398: the 'disordered' region

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

Similar variants

FLG p.Arg1798Ter Pathogenic/Likely pathogenic ★★ same condition
FLG p.Gln1790Ter Pathogenic ★★ same condition
FLG p.Gln355Ter Pathogenic ★★ same condition
FLG p.Ser2080Ter Pathogenic ★★ same condition
FLG p.Ser2554Ter Pathogenic/Likely pathogenic ★★ same condition
FLG p.Ser3296Ter Pathogenic ★★ same condition
FLG p.Arg1133Gln Uncertain significance ★★ ⚠ same condition
FLG p.Gln686Pro 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/flg-p-ser3398 (accessed [today's date]).

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