Is FLRT1 p.Ser146Leu (c.437C>T) pathogenic?

FLRT1 p.Ser146Leu (c.437C>T) is classified Uncertain significance in FLRT1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-01-29). Ultra-rare (popmax 0.09%, amr); Associated with peripheral neuropathy.

What condition is associated with FLRT1 p.Ser146Leu (c.437C>T)?

FLRT1 p.Ser146Leu (c.437C>T) is associated with peripheral neuropathy (ClinVar).

How common is FLRT1 p.Ser146Leu (c.437C>T) in the general population?

FLRT1 p.Ser146Leu (c.437C>T) is ultra-rare (popmax 0.09%, amr) (gnomAD).

FLRT1 p.Ser146Leu

c.437C>T · rs756250929 · VCV579757

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.09%, amr)

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	0.246	benign-leaning
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 7.7	GERP 2, phastCons 1
Regional constraint	o/e 0.78	unconstrained · MANE · 2,021 bp · p 5.7e-12 · regional, not allelic
Overall
CADD	25.0	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.09% Admixed American · 54/60,012 alleles

Filtering AF 0.0708% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0639%

Overall 0.00545% 88/1,613,696 alleles · ultra-rare exomes 81/1,461,500 · genomes 7/152,196 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.09%	1,111
Ashkenazi Jewishnot grpmax-eligible	0.054%	1,851
Remaining individualsnot grpmax-eligible	0.008%	12,496
African / African-American	0.00267%	37,471
South Asian	0.0022%	45,542
Finnishnot grpmax-eligible	0.00157%	63,662
European (non-Finnish)	0.000678%	147,504

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.Ser146Leu
Coding: c.437C>T
MANE Select: NM_013280
dbSNP: rs756250929
Type: single nucleotide variant
Location: chr11:64116704 (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-ser146leu (accessed [today's date]).

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