Is FLRT1 p.Asp136Gly (c.407A>G) pathogenic?

FLRT1 p.Asp136Gly (c.407A>G) is classified Likely benign in FLRT1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2022-08-15). Rare (popmax 0.261%, nfe); Associated with peripheral neuropathy.

What condition is associated with FLRT1 p.Asp136Gly (c.407A>G)?

FLRT1 p.Asp136Gly (c.407A>G) is associated with peripheral neuropathy (ClinVar).

How common is FLRT1 p.Asp136Gly (c.407A>G) in the general population?

FLRT1 p.Asp136Gly (c.407A>G) is rare (popmax 0.261%, nfe) (gnomAD).

FLRT1 p.Asp136Gly

c.407A>G · rs116999073 · VCV461802

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.261%, nfe)

Conditions

peripheral neuropathy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.488	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.1	GERP 2, phastCons 1
Regional constraint	o/e 0.78	unconstrained · MANE · 2,021 bp · p 5.7e-12 · regional, not allelic
Overall
CADD	23.1	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.261% European (non-Finnish) · 3,081/1,180,028 alleles

Filtering AF 0.253% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.25%

Overall 0.204% 3,292/1,613,982 alleles · rare exomes 3,076/1,461,658 · genomes 216/152,324 · joint denominator

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	0.768%	130
European (non-Finnish)grpmax	0.261%	383
Remaining individualsnot grpmax-eligible	0.149%	672
Ashkenazi Jewishnot grpmax-eligible	0.0979%	1,021
Finnishnot grpmax-eligible	0.0564%	1,773
African / African-American	0.0346%	2,886
Admixed American	0.03%	3,335
South Asian	0.0022%	45,541

Amish 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.Asp136Gly
Coding: c.407A>G
MANE Select: NM_013280
dbSNP: rs116999073
Type: single nucleotide variant
Location: chr11:64116674 (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-asp136gly (accessed [today's date]).

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