Is FLRT1 p.Val577Leu (c.1729G>C) pathogenic?

FLRT1 p.Val577Leu (c.1729G>C) is classified Uncertain significance in FLRT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2017-04-25). Very rare (popmax 0.00169%, nfe); Associated with peripheral neuropathy.

What condition is associated with FLRT1 p.Val577Leu (c.1729G>C)?

FLRT1 p.Val577Leu (c.1729G>C) is associated with peripheral neuropathy (ClinVar).

How common is FLRT1 p.Val577Leu (c.1729G>C) in the general population?

FLRT1 p.Val577Leu (c.1729G>C) is very rare (popmax 0.00169%, nfe) (gnomAD).

FLRT1 p.Val577Leu

c.1729G>C · rs140274429 · VCV461796

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00169%, 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	0.075	moderately benign-leaning
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 5.2	GERP -0.33, phastCons 1
Regional constraint	o/e 0.78	unconstrained · MANE · 2,021 bp · p 5.7e-12 · regional, not allelic
Overall
CADD	15.95	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00169% European (non-Finnish) · 20/1,179,998 alleles

Filtering AF 0.00111% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0009%

Overall 0.00136% 22/1,613,668 alleles · very rare exomes 21/1,461,450 · genomes 1/152,218 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00169%	59,000
Remaining individualsnot grpmax-eligible	0.0016%	62,484
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.Val577Leu
Coding: c.1729G>C
MANE Select: NM_013280
dbSNP: rs140274429
Type: single nucleotide variant
Location: chr11:64117996 (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-val577leu (accessed [today's date]).

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