Is FLG p.Asp2525= (c.7575C>T) pathogenic?

FLG p.Asp2525= (c.7575C>T) is classified Likely benign in FLG (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-10-19). Low-frequency (popmax 3.12%, afr).

How common is FLG p.Asp2525= (c.7575C>T) in the general population?

FLG p.Asp2525= (c.7575C>T) is low-frequency (popmax 3.12%, afr) (gnomAD).

FLG p.Asp2525=

c.7575C>T · rs74338867 · VCV1207910

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

low-frequency (popmax 3.12%, 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 -3.1	GERP -2.6
Overall
CADD	4.098	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 3.12% African / African-American · 2,326/74,660 alleles

Filtering AF 3.01% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.97%

Overall 0.168% 2,710/1,613,336 alleles · low-frequency exomes 1,351/1,461,872 · genomes 1,359/151,464 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	3.12%	32
Remaining individualsnot grpmax-eligible	0.235%	425
Admixed American	0.234%	428
East Asian	0.076%	1,316
Middle Eastern	0.033%	3,030
South Asian	0.011%	9,104
European (non-Finnish)	0.00432%	23,136

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.Asp2525=
Coding: c.7575C>T
MANE Select: NM_002016
dbSNP: rs74338867
Type: single nucleotide variant
Location: chr1:152307311 (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-asp2525 (accessed [today's date]).

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