Is FLRT1 p.Arg615= (c.1845C>T) pathogenic?

FLRT1 p.Arg615= (c.1845C>T) is classified Likely benign in FLRT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-06). Ultra-rare (popmax 0.0726%, sas); Associated with peripheral neuropathy.

What condition is associated with FLRT1 p.Arg615= (c.1845C>T)?

FLRT1 p.Arg615= (c.1845C>T) is associated with peripheral neuropathy (ClinVar).

How common is FLRT1 p.Arg615= (c.1845C>T) in the general population?

FLRT1 p.Arg615= (c.1845C>T) is ultra-rare (popmax 0.0726%, sas) (gnomAD).

FLRT1 p.Arg615=

c.1845C>T · VCV3672667

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0726%, sas)

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 -16	GERP -4
Overall
CADD	0.021	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0726% South Asian · 66/90,970 alleles

Filtering AF 0.0584% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0534%

Overall 0.00596% 96/1,611,370 alleles · ultra-rare exomes 83/1,459,002 · genomes 13/152,368 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0726%	1,378
Middle Eastern	0.0661%	1,514
Remaining individualsnot grpmax-eligible	0.00962%	10,391
East Asian	0.0067%	14,933
European (non-Finnish)	0.00144%	69,296

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.Arg615=
Coding: c.1845C>T
MANE Select: NM_013280
Type: single nucleotide variant
Location: chr11:64118112 (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.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
FLRT1 p.Arg592Trp 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-arg615 (accessed [today's date]).

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