Is FLG p.Arg3445= (c.10335G>A) pathogenic?

FLG p.Arg3445= (c.10335G>A) is classified Likely benign in FLG (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-01). Rare (popmax 0.716%, eas).

How common is FLG p.Arg3445= (c.10335G>A) in the general population?

FLG p.Arg3445= (c.10335G>A) is rare (popmax 0.716%, eas) (gnomAD).

FLG p.Arg3445=

c.10335G>A · VCV3770723

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.716%, eas)

⚠ 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 -15	GERP -3.1
Overall
CADD	0.244	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.716% East Asian · 300/41,902 alleles

Filtering AF 0.649% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.623%

Overall 0.129% 2,051/1,585,610 alleles · rare exomes 1,564/1,437,780 · genomes 487/147,830 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.716%	140
South Asian	0.384%	260
Amishnot grpmax-eligible	0.346%	289
Middle Eastern	0.22%	454
Ashkenazi Jewishnot grpmax-eligible	0.193%	517
Admixed American	0.188%	533
Remaining individualsnot grpmax-eligible	0.121%	829
European (non-Finnish)	0.0942%	1,061
Finnishnot grpmax-eligible	0.0489%	2,044
African / African-American	0.0485%	2,061

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.Arg3445=
Coding: c.10335G>A
MANE Select: NM_002016
Type: single nucleotide variant
Location: chr1:152304551 (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-arg3445 (accessed [today's date]).

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