Is FLRT1 p.Tyr600Cys (c.1799A>G) pathogenic?

FLRT1 p.Tyr600Cys (c.1799A>G) is classified Likely benign in FLRT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-06). Rare (popmax 0.417%, sas); Associated with peripheral neuropathy.

What condition is associated with FLRT1 p.Tyr600Cys (c.1799A>G)?

FLRT1 p.Tyr600Cys (c.1799A>G) is associated with peripheral neuropathy (ClinVar).

How common is FLRT1 p.Tyr600Cys (c.1799A>G) in the general population?

FLRT1 p.Tyr600Cys (c.1799A>G) is rare (popmax 0.417%, sas) (gnomAD).

FLRT1 p.Tyr600Cys

c.1799A>G · rs368223580 · VCV1112150

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.417%, sas)

Conditions

peripheral neuropathy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.65	pathogenic-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2, phastCons 1
Regional constraint	o/e 0.78	unconstrained · MANE · 2,021 bp · p 5.7e-12 · regional, not allelic
Overall
CADD	26.7	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.417% South Asian · 380/91,034 alleles

Filtering AF 0.383% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.369%

Overall 0.03% 484/1,613,068 alleles · rare exomes 449/1,460,720 · genomes 35/152,348 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.417%	240
Middle Eastern	0.231%	433
Remaining individualsnot grpmax-eligible	0.0416%	2,402
Admixed American	0.0133%	7,500
European (non-Finnish)	0.00449%	22,254
African / African-American	0.00266%	37,528
East Asian	0.00223%	44,854

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.Tyr600Cys
Coding: c.1799A>G
MANE Select: NM_013280
dbSNP: rs368223580
Type: single nucleotide variant
Location: chr11:64118066 (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.Tyr600Asn 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-tyr600cys (accessed [today's date]).

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