Is FLG p.Ala508= (c.1524G>A) pathogenic?

FLG p.Ala508= (c.1524G>A) is classified Likely benign in FLG (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-02-01). Ultra-rare (popmax 0.0444%, afr).

How common is FLG p.Ala508= (c.1524G>A) in the general population?

FLG p.Ala508= (c.1524G>A) is ultra-rare (popmax 0.0444%, afr) (gnomAD).

FLG p.Ala508=

c.1524G>A · rs148161383 · VCV2639319

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0444%, 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 -20	GERP -3.2
Overall
CADD	4.635	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0444% African / African-American · 33/74,304 alleles

Filtering AF 0.0324% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0283%

Overall 0.0118% 191/1,612,776 alleles · ultra-rare exomes 158/1,461,596 · genomes 33/151,180 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0444%	2,252
Remaining individualsnot grpmax-eligible	0.0272%	3,674
European (non-Finnish)	0.0114%	8,804
Admixed American	0.005%	19,985
Finnishnot grpmax-eligible	0.00313%	31,989
South Asian	0.0022%	45,505

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.Ala508=
Coding: c.1524G>A
MANE Select: NM_002016
dbSNP: rs148161383
Type: single nucleotide variant
Location: chr1:152313362 (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-ala508 (accessed [today's date]).

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