Is FLRT1 p.Arg130Gln (c.389G>A) pathogenic?

FLRT1 p.Arg130Gln (c.389G>A) is classified Uncertain significance in FLRT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-10-31). Ultra-rare (popmax 0.0166%, mid); Associated with peripheral neuropathy.

What condition is associated with FLRT1 p.Arg130Gln (c.389G>A)?

FLRT1 p.Arg130Gln (c.389G>A) is associated with peripheral neuropathy (ClinVar).

How common is FLRT1 p.Arg130Gln (c.389G>A) in the general population?

FLRT1 p.Arg130Gln (c.389G>A) is ultra-rare (popmax 0.0166%, mid) (gnomAD).

FLRT1 p.Arg130Gln

c.389G>A · rs201296024 · VCV1002428

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0166%, mid)

Conditions

peripheral neuropathy

⚠ 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.
REVEL	0.269	benign-leaning
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 9.9	GERP -1.6, phastCons 1
Regional constraint	o/e 0.78	unconstrained · MANE · 2,021 bp · p 5.7e-12 · regional, not allelic
Overall
CADD	25.4	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0166% Middle Eastern · 1/6,030 alleles

Filtering AF 0.00428% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00295%

Overall 0.0018% 29/1,613,794 alleles · ultra-rare exomes 26/1,461,652 · genomes 3/152,142 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0166%	6,030
Admixed American	0.01%	10,002
Remaining individualsnot grpmax-eligible	0.0032%	31,248
East Asian	0.00223%	44,854
European (non-Finnish)	0.00153%	65,553
South Asian	0.0011%	91,072

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: FLRT1
Protein: p.Arg130Gln
Coding: c.389G>A
MANE Select: NM_013280
dbSNP: rs201296024
Type: single nucleotide variant
Location: chr11:64116656 (GRCh38)

Full FLRT1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

peripheral neuropathy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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/flrt1-p-arg130gln (accessed [today's date]).

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