Is FLG2 p.Gln2000= (c.6000A>G) pathogenic?

FLG2 p.Gln2000= (c.6000A>G) is classified Likely benign in FLG2 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-06-01). Ultra-rare (popmax 0.0104%, afr).

How common is FLG2 p.Gln2000= (c.6000A>G) in the general population?

FLG2 p.Gln2000= (c.6000A>G) is ultra-rare (popmax 0.0104%, afr) (gnomAD).

FLG2 p.Gln2000=

c.6000A>G · VCV4872945

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0104%, 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 -15	GERP -0.72
Overall
CADD	0.451	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0104% African / African-American · 7/67,188 alleles

Filtering AF 0.00482% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00337%

Overall 0.00182% 29/1,591,428 alleles · ultra-rare exomes 8/1,460,546 · genomes 21/130,882 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0104%	9,598
Finnishnot grpmax-eligible	0.0032%	31,232
East Asian	0.00228%	43,934
Admixed American	0.00173%	57,960
Remaining individualsnot grpmax-eligible	0.00161%	62,122
European (non-Finnish)	0.00145%	68,922

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.Gln2000=
Coding: c.6000A>G
MANE Select: NM_001014342
Type: single nucleotide variant
Location: chr1:152351786 (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-gln2000 (accessed [today's date]).

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