Is FLG p.Ser2805= (c.8415G>A) pathogenic?

FLG p.Ser2805= (c.8415G>A) is classified Likely benign in FLG (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-11-25). Ultra-rare (popmax 0.033%, mid).

How common is FLG p.Ser2805= (c.8415G>A) in the general population?

FLG p.Ser2805= (c.8415G>A) is ultra-rare (popmax 0.033%, mid) (gnomAD).

FLG p.Ser2805=

c.8415G>A · rs367828510 · VCV2639258

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.033%, mid)

⚠ 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 -6.9	GERP -3
Overall
CADD	4.465	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.033% Middle Eastern · 2/6,062 alleles

Filtering AF 0.0204% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0195%

Overall 0.0197% 317/1,607,790 alleles · ultra-rare exomes 289/1,461,538 · genomes 28/146,252 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.033%	3,031
Finnishnot grpmax-eligible	0.0234%	4,267
European (non-Finnish)	0.0227%	4,402
Admixed American	0.0167%	5,992
Remaining individualsnot grpmax-eligible	0.0128%	7,806
African / African-American	0.00868%	11,519
South Asian	0.00659%	15,168
East Asian	0.00446%	22,428

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.Ser2805=
Coding: c.8415G>A
MANE Select: NM_002016
dbSNP: rs367828510
Type: single nucleotide variant
Location: chr1:152306471 (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-ser2805 (accessed [today's date]).

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