Is FLG p.Ser2732= (c.8196T>G) pathogenic?

FLG p.Ser2732= (c.8196T>G) is classified Likely benign in FLG (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-11-19). Very rare (popmax 0.00346%, amr).

How common is FLG p.Ser2732= (c.8196T>G) in the general population?

FLG p.Ser2732= (c.8196T>G) is very rare (popmax 0.00346%, amr) (gnomAD).

FLG p.Ser2732=

c.8196T>G · rs765382222 · VCV3025213

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00346%, amr)

⚠ 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 -14	GERP -3.2
Overall
CADD	2.395	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00346% Admixed American · 2/57,796 alleles

Filtering AF 0.00139% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00117%

Overall 0.00171% 27/1,575,118 alleles · very rare exomes 24/1,455,096 · genomes 3/120,022 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00346%	28,898
European (non-Finnish)	0.00206%	48,628
South Asian	0.00111%	89,910

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.Ser2732=
Coding: c.8196T>G
MANE Select: NM_002016
dbSNP: rs765382222
Type: single nucleotide variant
Location: chr1:152306690 (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-ser2732 (accessed [today's date]).

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