Is FLG2 p.Ser2020= (c.6060C>A) pathogenic?

FLG2 p.Ser2020= (c.6060C>A) is classified Likely benign in FLG2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-01). Very rare (popmax 0.00725%, afr).

How common is FLG2 p.Ser2020= (c.6060C>A) in the general population?

FLG2 p.Ser2020= (c.6060C>A) is very rare (popmax 0.00725%, afr) (gnomAD).

FLG2 p.Ser2020=

c.6060C>A · rs559508459 · VCV2639332

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00725%, afr)

⚠ 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 -6.8	GERP -2.5
Overall
CADD	0.482	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00725% African / African-American · 5/69,010 alleles

Filtering AF 0.00282% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00184%

Overall 0.001% 16/1,596,702 alleles · very rare exomes 4/1,459,340 · genomes 12/137,362 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00725%	13,802
East Asian	0.00457%	21,901
South Asian	0.00222%	45,063
Finnishnot grpmax-eligible	0.0016%	62,452
European (non-Finnish)	0.000511%	195,775

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: FLG2
Protein: p.Ser2020=
Coding: c.6060C>A
MANE Select: NM_001014342
dbSNP: rs559508459
Type: single nucleotide variant
Location: chr1:152351726 (GRCh38)

Full FLG2 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/flg2-p-ser2020 (accessed [today's date]).

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