Is FLG p.Asp2201= (c.6603T>C) pathogenic?

FLG p.Asp2201= (c.6603T>C) is classified Benign in FLG (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-07-09). Common (popmax 42%, afr) — too common for a highly-penetrant pathogenic allele.

FLG p.Asp2201=

Q: How common is FLG p.Asp2201= (c.6603T>C) in the general population?

FLG p.Asp2201= (c.6603T>C) is common (popmax 42%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.6603T>C · rs2338554 · VCV1182765

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 42%, afr) — 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 -11	GERP -2.3
Overall
CADD	0.583	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 42% African / African-American · 30,532/72,666 alleles

Filtering AF 41.6% ClinGen BA1/BS1 input FAF95, joint · FAF99 41.5%

Overall 18.2% 286,278/1,574,598 alleles · common exomes 252,004/1,433,024 · genomes 34,274/141,574 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	42%	2
East Asian	41.8%	2
Admixed American	32.4%	3
South Asian	31%	3
Ashkenazi Jewishnot grpmax-eligible	24.8%	4
Middle Eastern	24.2%	4
Remaining individualsnot grpmax-eligible	21.2%	5
Amishnot grpmax-eligible	15.9%	6
Finnishnot grpmax-eligible	14.6%	7
European (non-Finnish)	14%	7

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.Asp2201=
Coding: c.6603T>C
MANE Select: NM_002016
dbSNP: rs2338554
Type: single nucleotide variant
Location: chr1:152308283 (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-asp2201 (accessed [today's date]).

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