Is FLRT1 p.Thr454= (c.1362G>A) pathogenic?

FLRT1 p.Thr454= (c.1362G>A) is classified Likely benign in FLRT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-09-28). Very rare (popmax 0.00266%, afr); Associated with peripheral neuropathy.

What condition is associated with FLRT1 p.Thr454= (c.1362G>A)?

FLRT1 p.Thr454= (c.1362G>A) is associated with peripheral neuropathy (ClinVar).

How common is FLRT1 p.Thr454= (c.1362G>A) in the general population?

FLRT1 p.Thr454= (c.1362G>A) is very rare (popmax 0.00266%, afr) (gnomAD).

FLRT1 p.Thr454=

c.1362G>A · rs1590934167 · VCV1110522

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00266%, afr)

Conditions

peripheral neuropathy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -7.8	GERP -4
Overall
CADD	1.402	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00266% African / African-American · 2/75,072 alleles

Filtering AF 0.000442% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00026%

Overall 0.000868% 14/1,613,786 alleles · very rare exomes 14/1,461,434 · genomes 0/152,352 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00266%	37,536
East Asian	0.00223%	44,864
Admixed American	0.00167%	60,036
South Asian	0.0011%	91,080
European (non-Finnish)	0.000763%	131,114

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.Thr454=
Coding: c.1362G>A
MANE Select: NM_013280
dbSNP: rs1590934167
Type: single nucleotide variant
Location: chr11:64117629 (GRCh38)
Gene constraint: LOEUF 0.682 · pLI 0.14 (gnomAD)
Structure: AlphaFold pLDDT 73.46
Residue 454: the fibronectin type-iii domain

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.Thr454Pro Uncertain significance ★ same residue
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

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-thr454 (accessed [today's date]).

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