Is FLG p.Arg852= (c.2556G>A) pathogenic?

FLG p.Arg852= (c.2556G>A) is classified Likely benign in FLG (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-08). Rare (popmax 0.573%, afr).

How common is FLG p.Arg852= (c.2556G>A) in the general population?

FLG p.Arg852= (c.2556G>A) is rare (popmax 0.573%, afr) (gnomAD).

FLG p.Arg852=

c.2556G>A · rs71625190 · VCV4912212

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.573%, 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 -6.7	GERP -2.9
Overall
CADD	1.466	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.573% African / African-American · 345/60,158 alleles

Filtering AF 0.524% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.504%

Overall 0.0371% 583/1,569,660 alleles · rare exomes 13/1,445,208 · genomes 570/124,452 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.573%	174
Admixed American	0.122%	822
East Asian	0.0514%	1,947
South Asian	0.0475%	2,107
Ashkenazi Jewishnot grpmax-eligible	0.0387%	2,587
Finnishnot grpmax-eligible	0.0352%	2,840
Middle Eastern	0.0341%	2,935
Remaining individualsnot grpmax-eligible	0.0131%	7,617
European (non-Finnish)	0.00549%	18,213

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.Arg852=
Coding: c.2556G>A
MANE Select: NM_002016
dbSNP: rs71625190
Type: single nucleotide variant
Location: chr1:152312330 (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-arg852 (accessed [today's date]).

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