Is FLG p.Asp579= (c.1737C>T) pathogenic?

FLG p.Asp579= (c.1737C>T) is classified Likely benign in FLG (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-06-01). Ultra-rare (popmax 0.0997%, nfe).

How common is FLG p.Asp579= (c.1737C>T) in the general population?

FLG p.Asp579= (c.1737C>T) is ultra-rare (popmax 0.0997%, nfe) (gnomAD).

FLG p.Asp579=

c.1737C>T · rs145104949 · VCV2639315

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0997%, nfe)

⚠ 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 -6.7	GERP -2.2
Overall
CADD	3.059	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0997% European (non-Finnish) · 1,176/1,179,994 alleles

Filtering AF 0.0949% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.093%

Overall 0.0806% 1,301/1,613,804 alleles · ultra-rare exomes 1,175/1,461,888 · genomes 126/151,916 · joint denominator

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	0.987%	101
European (non-Finnish)grpmax	0.0997%	1,003
Remaining individualsnot grpmax-eligible	0.0624%	1,603
Admixed American	0.05%	2,000
Finnishnot grpmax-eligible	0.0375%	2,667
African / African-American	0.0214%	4,677
Middle Eastern	0.0165%	6,062
Ashkenazi Jewishnot grpmax-eligible	0.0135%	7,401
South Asian	0.0022%	45,537

Amish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Asp579=
Coding: c.1737C>T
MANE Select: NM_002016
dbSNP: rs145104949
Type: single nucleotide variant
Location: chr1:152313149 (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-asp579 (accessed [today's date]).

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