Is FLG2 p.Ser920= (c.2760T>C) pathogenic?

FLG2 p.Ser920= (c.2760T>C) is classified Benign in FLG2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2021-05-04). Common (popmax 16.2%, eas) — too common for a highly-penetrant pathogenic allele.

FLG2 p.Ser920=

Q: How common is FLG2 p.Ser920= (c.2760T>C) in the general population?

FLG2 p.Ser920= (c.2760T>C) is common (popmax 16.2%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.2760T>C · rs138997916 · VCV1271582

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 16.2%, eas) — too common for a highly-penetrant pathogenic allele

⚠ 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 -1.6	GERP -1.7
Overall
CADD	1.322	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 16.2% East Asian · 3,879/23,880 alleles

Filtering AF 15.8% ClinGen BA1/BS1 input FAF95, joint · FAF99 15.6%

Overall 2.23% 31,731/1,422,910 alleles · common exomes 25,026/1,301,728 · genomes 6,705/121,182 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	16.2%	6
Amishnot grpmax-eligible	7.55%	13
Admixed American	7.51%	13
South Asian	6.26%	16
Ashkenazi Jewishnot grpmax-eligible	5.8%	17
Middle Eastern	4.93%	20
Finnishnot grpmax-eligible	4.22%	24
Remaining individualsnot grpmax-eligible	2.79%	36
European (non-Finnish)	1.33%	75
African / African-American	0.852%	117

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.Ser920=
Coding: c.2760T>C
MANE Select: NM_001014342
dbSNP: rs138997916
Type: single nucleotide variant
Location: chr1:152355026 (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-ser920 (accessed [today's date]).

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