Is FLRT1 p.Thr13Arg (c.38C>G) pathogenic?

FLRT1 p.Thr13Arg (c.38C>G) is classified Uncertain significance in FLRT1 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2023-11-06). Rare (popmax 0.188%, nfe); Associated with peripheral neuropathy.

What condition is associated with FLRT1 p.Thr13Arg (c.38C>G)?

FLRT1 p.Thr13Arg (c.38C>G) is associated with peripheral neuropathy (ClinVar).

How common is FLRT1 p.Thr13Arg (c.38C>G) in the general population?

FLRT1 p.Thr13Arg (c.38C>G) is rare (popmax 0.188%, nfe) (gnomAD).

FLRT1 p.Thr13Arg

c.38C>G · rs139768227 · VCV461801

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

rare (popmax 0.188%, nfe)

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	0.088	moderately benign-leaning
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 4.7	GERP 1.7, phastCons 0.86
Regional constraint	o/e 0.78	unconstrained · MANE · 2,021 bp · p 5.7e-12 · regional, not allelic
Overall
CADD	21.3	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.188% European (non-Finnish) · 2,211/1,178,140 alleles

Filtering AF 0.181% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.178%

Overall 0.152% 2,449/1,606,438 alleles · rare exomes 2,329/1,454,084 · genomes 120/152,354 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.188%	533
Remaining individualsnot grpmax-eligible	0.125%	799
South Asian	0.114%	878
Ashkenazi Jewishnot grpmax-eligible	0.0983%	1,017
Middle Eastern	0.0661%	1,514
African / African-American	0.02%	4,999
Admixed American	0.0101%	9,914
Finnishnot grpmax-eligible	0.00501%	19,979

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.Thr13Arg
Coding: c.38C>G
MANE Select: NM_013280
dbSNP: rs139768227
Type: single nucleotide variant
Location: chr11:64116305 (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-thr13arg (accessed [today's date]).

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