Is FLRT1 p.Ile573= (c.1719C>T) pathogenic?

FLRT1 p.Ile573= (c.1719C>T) is classified Likely benign in FLRT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-04-21). Ultra-rare (popmax 0.014%, nfe); Associated with peripheral neuropathy.

What condition is associated with FLRT1 p.Ile573= (c.1719C>T)?

FLRT1 p.Ile573= (c.1719C>T) is associated with peripheral neuropathy (ClinVar).

How common is FLRT1 p.Ile573= (c.1719C>T) in the general population?

FLRT1 p.Ile573= (c.1719C>T) is ultra-rare (popmax 0.014%, nfe) (gnomAD).

FLRT1 p.Ile573=

c.1719C>T · rs372121350 · VCV1156519

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.014%, nfe)

Conditions

peripheral neuropathy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 2.7	GERP -0.6, phastCons 1
Overall
CADD	10.38	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.014% European (non-Finnish) · 165/1,180,024 alleles

Filtering AF 0.0122% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0116%

Overall 0.0109% 176/1,613,718 alleles · ultra-rare exomes 166/1,461,472 · genomes 10/152,246 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.014%	7,152
Remaining individualsnot grpmax-eligible	0.0112%	8,926
South Asian	0.00329%	30,365
African / African-American	0.00133%	74,946

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.Ile573=
Coding: c.1719C>T
MANE Select: NM_013280
dbSNP: rs372121350
Type: single nucleotide variant
Location: chr11:64117986 (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-ile573 (accessed [today's date]).

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