Is FLRT1 p.Thr395Met (c.1184C>T) pathogenic?

FLRT1 p.Thr395Met (c.1184C>T) is classified Likely benign in FLRT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-17). Rare (popmax 0.261%, nfe); Associated with peripheral neuropathy.

What condition is associated with FLRT1 p.Thr395Met (c.1184C>T)?

FLRT1 p.Thr395Met (c.1184C>T) is associated with peripheral neuropathy (ClinVar).

How common is FLRT1 p.Thr395Met (c.1184C>T) in the general population?

FLRT1 p.Thr395Met (c.1184C>T) is rare (popmax 0.261%, nfe) (gnomAD).

FLRT1 p.Thr395Met

c.1184C>T · rs138676741 · VCV461793

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.261%, 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	0.22	benign-leaning
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 5.9	GERP 0.8, 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) · 3,076/1,179,226 alleles

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

Overall 0.22% 3,550/1,613,004 alleles · rare exomes 3,296/1,460,626 · genomes 254/152,378 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.261%	383
South Asian	0.207%	484
Remaining individualsnot grpmax-eligible	0.205%	488
Finnishnot grpmax-eligible	0.131%	761
Admixed American	0.065%	1,538
African / African-American	0.0426%	2,346
Middle Eastern	0.033%	3,030
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,556

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.Thr395Met
Coding: c.1184C>T
MANE Select: NM_013280
dbSNP: rs138676741
Type: single nucleotide variant
Location: chr11:64117451 (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-thr395met (accessed [today's date]).

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