Is FLRT1 p.Arg238= (c.714C>T) pathogenic?

FLRT1 p.Arg238= (c.714C>T) is classified Benign in FLRT1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-11-24). Common (popmax 52.4%, eas) — too common for a highly-penetrant pathogenic allele; Associated with peripheral neuropathy.

What condition is associated with FLRT1 p.Arg238= (c.714C>T)?

FLRT1 p.Arg238= (c.714C>T) is associated with peripheral neuropathy (ClinVar).

FLRT1 p.Arg238=

Q: How common is FLRT1 p.Arg238= (c.714C>T) in the general population?

FLRT1 p.Arg238= (c.714C>T) is common (popmax 52.4%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.714C>T · rs3751120 · VCV1165132

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 52.4%, eas) — too common for a highly-penetrant pathogenic allele

Conditions

peripheral neuropathy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.3	GERP -0.43, phastCons 1
Overall
CADD	11.31	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 52.4% East Asian · 23,500/44,824 alleles

Filtering AF 51.9% ClinGen BA1/BS1 input FAF95, joint · FAF99 51.6%

Overall 12.1% 195,529/1,611,884 alleles · common exomes 160,570/1,459,726 · genomes 34,959/152,158 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	52.4%	2
African / African-American	52.1%	2
Admixed American	21.7%	5
South Asian	18.6%	5
Middle Eastern	16.1%	6
Remaining individualsnot grpmax-eligible	15.2%	7
Ashkenazi Jewishnot grpmax-eligible	14.1%	7
Finnishnot grpmax-eligible	10%	10
European (non-Finnish)	6.96%	14
Amishnot grpmax-eligible	4.82%	21

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.Arg238=
Coding: c.714C>T
MANE Select: NM_013280
dbSNP: rs3751120
Type: single nucleotide variant
Location: chr11:64116981 (GRCh38)
Gene constraint: LOEUF 0.682 · pLI 0.14 (gnomAD)
Structure: AlphaFold pLDDT 73.46

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

Similar variants

FLRT1 p.Arg238His Uncertain significance ★ same residue
FLRT1 p.Ala148Gly Uncertain significance ★★ same condition
FLRT1 p.Ala461Thr Uncertain significance ★★ same condition
FLRT1 p.Arg149Cys Uncertain significance ★★ same condition
FLRT1 p.Arg326Lys Uncertain significance ★★ same condition
FLRT1 p.Arg452His Uncertain significance ★★ same condition
FLRT1 p.Arg586Gln Uncertain significance ★★ same condition
FLRT1 p.Arg592Gln Uncertain significance ★★ same condition

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-arg238 (accessed [today's date]).

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