Is FLG p.Ser1630= (c.4890C>T) pathogenic?

FLG p.Ser1630= (c.4890C>T) is classified Benign/Likely benign in FLG (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-09-01). Low-frequency (popmax 1.02%, sas).

How common is FLG p.Ser1630= (c.4890C>T) in the general population?

FLG p.Ser1630= (c.4890C>T) is low-frequency (popmax 1.02%, sas) (gnomAD).

FLG p.Ser1630=

c.4890C>T · VCV4280983

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.02%, sas)

⚠ 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 -10	GERP -2.5
Overall
CADD	2.096	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.02% South Asian · 927/91,062 alleles

Filtering AF 0.964% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.942%

Overall 0.0619% 999/1,613,950 alleles · low-frequency exomes 946/1,461,890 · genomes 53/152,060 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	1.02%	98
Remaining individualsnot grpmax-eligible	0.106%	947
Middle Eastern	0.033%	3,031
African / African-American	0.00133%	74,948
European (non-Finnish)	0.000254%	393,335

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.Ser1630=
Coding: c.4890C>T
MANE Select: NM_002016
Type: single nucleotide variant
Location: chr1:152309996 (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-ser1630 (accessed [today's date]).

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