Is FLG p.Ser1129= (c.3387T>C) pathogenic?

FLG p.Ser1129= (c.3387T>C) is classified Benign in FLG (ClinVar, Multiple submitters, 3 submitters; last evaluated 2023-04-11). Common (popmax 61.8%, eas) — too common for a highly-penetrant pathogenic allele; Associated with ichthyosis vulgaris.

What condition is associated with FLG p.Ser1129= (c.3387T>C)?

FLG p.Ser1129= (c.3387T>C) is associated with ichthyosis vulgaris (ClinVar).

FLG p.Ser1129=

Q: How common is FLG p.Ser1129= (c.3387T>C) in the general population?

FLG p.Ser1129= (c.3387T>C) is common (popmax 61.8%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.3387T>C · rs66831674 · VCV1245184

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Common

common (popmax 61.8%, eas) — too common for a highly-penetrant pathogenic allele

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; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -11	GERP -3.5
Overall
CADD	0.675	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 61.8% East Asian · 27,621/44,696 alleles

Filtering AF 61.2% ClinGen BA1/BS1 input FAF95, joint · FAF99 60.9%

Overall 22% 354,420/1,613,096 alleles · common exomes 308,789/1,461,622 · genomes 45,631/151,474 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	61.8%	2
African / African-American	47.6%	2
Admixed American	43.7%	2
South Asian	41.6%	2
Ashkenazi Jewishnot grpmax-eligible	30.6%	3
Middle Eastern	30.3%	3
Remaining individualsnot grpmax-eligible	26.1%	4
Amishnot grpmax-eligible	19.7%	5
Finnishnot grpmax-eligible	17.8%	6
European (non-Finnish)	16%	6

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.Ser1129=
Coding: c.3387T>C
MANE Select: NM_002016
dbSNP: rs66831674
Type: single nucleotide variant
Location: chr1:152311499 (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-ser1129 (accessed [today's date]).

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