Is FLRT1 p.Ala549Val (c.1646C>T) pathogenic?

FLRT1 p.Ala549Val (c.1646C>T) is classified Uncertain significance in FLRT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-02-04). Very rare (popmax 0.00763%, nfe); Associated with peripheral neuropathy.

What condition is associated with FLRT1 p.Ala549Val (c.1646C>T)?

FLRT1 p.Ala549Val (c.1646C>T) is associated with peripheral neuropathy (ClinVar).

How common is FLRT1 p.Ala549Val (c.1646C>T) in the general population?

FLRT1 p.Ala549Val (c.1646C>T) is very rare (popmax 0.00763%, nfe) (gnomAD).

FLRT1 p.Ala549Val

c.1646C>T · rs148484621 · VCV835656

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00763%, nfe)

Conditions

peripheral neuropathy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.025	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -4.5	GERP -3.4
Regional constraint	o/e 0.78	unconstrained · MANE · 2,021 bp · p 5.7e-12 · regional, not allelic
Overall
CADD	6.156	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00763% European (non-Finnish) · 90/1,179,910 alleles

Filtering AF 0.00631% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00584%

Overall 0.00626% 101/1,613,674 alleles · very rare exomes 90/1,461,412 · genomes 11/152,262 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00763%	13,110
Admixed American	0.00667%	15,000
Remaining individualsnot grpmax-eligible	0.0064%	15,621
Finnishnot grpmax-eligible	0.00314%	31,889
East Asian	0.00223%	44,894

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.Ala549Val
Coding: c.1646C>T
MANE Select: NM_013280
dbSNP: rs148484621
Type: single nucleotide variant
Location: chr11:64117913 (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.Ala549Gly 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-ala549val (accessed [today's date]).

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