Is FLRT1 p.Thr19= (c.57G>A) pathogenic?

FLRT1 p.Thr19= (c.57G>A) is classified Benign in FLRT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-17). Rare (popmax 0.903%, sas); Associated with peripheral neuropathy.

What condition is associated with FLRT1 p.Thr19= (c.57G>A)?

FLRT1 p.Thr19= (c.57G>A) is associated with peripheral neuropathy (ClinVar).

How common is FLRT1 p.Thr19= (c.57G>A) in the general population?

FLRT1 p.Thr19= (c.57G>A) is rare (popmax 0.903%, sas) (gnomAD).

FLRT1 p.Thr19=

c.57G>A · rs547325012 · VCV1166605

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.903%, sas)

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 -3.4	GERP -3.3
Overall
CADD	0.684	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.903% South Asian · 818/90,566 alleles

Filtering AF 0.852% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.831%

Overall 0.0546% 879/1,609,738 alleles · rare exomes 834/1,457,460 · genomes 45/152,278 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.903%	111
Remaining individualsnot grpmax-eligible	0.0609%	1,642
Middle Eastern	0.033%	3,030
Admixed American	0.0134%	7,460
African / African-American	0.00801%	12,492
European (non-Finnish)	0.000594%	168,407

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.Thr19=
Coding: c.57G>A
MANE Select: NM_013280
dbSNP: rs547325012
Type: single nucleotide variant
Location: chr11:64116324 (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.Thr19Met 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-thr19 (accessed [today's date]).

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