Is FLG p.Ser495= (c.1485G>A) pathogenic?

FLG p.Ser495= (c.1485G>A) is classified Benign in FLG (ClinVar, Multiple submitters, 3 submitters; last evaluated 2019-02-04). Common (popmax 5.11%, afr) — too common for a highly-penetrant pathogenic allele.

FLG p.Ser495=

Q: How common is FLG p.Ser495= (c.1485G>A) in the general population?

FLG p.Ser495= (c.1485G>A) is common (popmax 5.11%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1485G>A · rs75530805 · VCV1226244

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Common

common (popmax 5.11%, 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 -20	GERP -3.5
Overall
CADD	0.983	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 5.11% African / African-American · 3,823/74,762 alleles

Filtering AF 4.98% ClinGen BA1/BS1 input FAF95, joint · FAF99 4.92%

Overall 0.271% 4,374/1,613,494 alleles · common exomes 2,142/1,461,782 · genomes 2,232/151,712 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	5.11%	20
Middle Eastern	0.462%	216
Admixed American	0.372%	269
Remaining individualsnot grpmax-eligible	0.326%	306
South Asian	0.0198%	5,058
East Asian	0.0134%	7,467
European (non-Finnish)	0.0061%	16,387

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.Ser495=
Coding: c.1485G>A
MANE Select: NM_002016
dbSNP: rs75530805
Type: single nucleotide variant
Location: chr1:152313401 (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-ser495 (accessed [today's date]).

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