Is FLRT1 p.Arg615Cys (c.1843C>T) pathogenic?

FLRT1 p.Arg615Cys (c.1843C>T) is classified Likely benign in FLRT1 (ClinVar, Single submitter, 2 submitters; last evaluated 2024-02-24). Rare (popmax 0.148%, nfe); Associated with peripheral neuropathy.

What condition is associated with FLRT1 p.Arg615Cys (c.1843C>T)?

FLRT1 p.Arg615Cys (c.1843C>T) is associated with peripheral neuropathy (ClinVar).

How common is FLRT1 p.Arg615Cys (c.1843C>T) in the general population?

FLRT1 p.Arg615Cys (c.1843C>T) is rare (popmax 0.148%, nfe) (gnomAD).

FLRT1 p.Arg615Cys

c.1843C>T · rs61735088 · VCV704987

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

rare (popmax 0.148%, 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	0.292	indeterminate
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 3.3	GERP -0.59, phastCons 1
Regional constraint	o/e 0.78	unconstrained · MANE · 2,021 bp · p 5.7e-12 · regional, not allelic
Overall
CADD	25.6	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.148% European (non-Finnish) · 1,748/1,178,206 alleles

Filtering AF 0.143% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.14%

Overall 0.132% 2,126/1,611,600 alleles · rare exomes 1,977/1,459,250 · genomes 149/152,350 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.431%	232
European (non-Finnish)grpmax	0.148%	674
Remaining individualsnot grpmax-eligible	0.101%	990
African / African-American	0.0293%	3,410
Middle Eastern	0.0165%	6,056
Admixed American	0.0133%	7,495
South Asian	0.00989%	10,110

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Arg615Cys
Coding: c.1843C>T
MANE Select: NM_013280
dbSNP: rs61735088
Type: single nucleotide variant
Location: chr11:64118110 (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-arg615cys (accessed [today's date]).

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