Is FLG p.Arg2829His (c.8486G>A) pathogenic?

FLG p.Arg2829His (c.8486G>A) is classified Likely benign in FLG (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-11-11). AlphaMissense: likely benign (0.0742); Rare (popmax 0.331%, afr).

How common is FLG p.Arg2829His (c.8486G>A) in the general population?

FLG p.Arg2829His (c.8486G>A) is rare (popmax 0.331%, afr) (gnomAD).

What do computational predictors say about FLG p.Arg2829His (c.8486G>A)?

AlphaMissense predicts likely benign (score 0.0742) — an in-silico prediction, not a clinical call.

FLG p.Arg2829His

c.8486G>A · rs140749305 · VCV599456

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0742 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.331%, afr)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

⚠ 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
AlphaMissense	0.0742	likely benign
REVEL	0.009	strongly benign-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this tolerated; SaProt makes no call.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -6.1	GERP -2.3
Regional constraint	o/e 0.91	unconstrained · MANE · 205 bp · p 0.38 · regional, not allelic
Overall
CADD	0.113	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.331% African / African-American · 211/63,786 alleles

Filtering AF 0.294% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.28%

Overall 0.117% 1,880/1,601,126 alleles · rare exomes 1,719/1,459,352 · genomes 161/141,774 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.331%	302
European (non-Finnish)	0.128%	779
Remaining individualsnot grpmax-eligible	0.108%	930
Admixed American	0.0603%	1,658
Finnishnot grpmax-eligible	0.05%	1,999
Middle Eastern	0.0331%	3,024
East Asian	0.0223%	4,486
Ashkenazi Jewishnot grpmax-eligible	0.0101%	9,854
South Asian	0.00549%	18,207

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.Arg2829His
Coding: c.8486G>A
MANE Select: NM_002016
dbSNP: rs140749305
Type: single nucleotide variant
Location: chr1:152306400 (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-arg2829his (accessed [today's date]).

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