Is FLRT1 p.Tyr516= (c.1548C>T) pathogenic?

FLRT1 p.Tyr516= (c.1548C>T) is classified Benign in FLRT1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-08). Common (popmax 16.5%, nfe) — too common for a highly-penetrant pathogenic allele; Associated with peripheral neuropathy.

What condition is associated with FLRT1 p.Tyr516= (c.1548C>T)?

FLRT1 p.Tyr516= (c.1548C>T) is associated with peripheral neuropathy (ClinVar).

FLRT1 p.Tyr516=

Q: How common is FLRT1 p.Tyr516= (c.1548C>T) in the general population?

FLRT1 p.Tyr516= (c.1548C>T) is common (popmax 16.5%, nfe) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1548C>T · rs947939 · VCV1170348

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 16.5%, nfe) — too common for a highly-penetrant pathogenic allele

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 -8	GERP -3.7
Overall
CADD	0.373	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 16.5% European (non-Finnish) · 194,260/1,179,986 alleles

Filtering AF 16.4% ClinGen BA1/BS1 input FAF95, joint · FAF99 16.4%

Overall 14.3% 230,513/1,614,098 alleles · common exomes 214,585/1,461,756 · genomes 15,928/152,342 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	16.5%	6
Amishnot grpmax-eligible	13.9%	7
Remaining individualsnot grpmax-eligible	12.4%	8
Finnishnot grpmax-eligible	12.1%	8
East Asian	9.71%	10
Admixed American	8.6%	12
South Asian	7.1%	14
Ashkenazi Jewishnot grpmax-eligible	7.06%	14
Middle Eastern	5.61%	18
African / African-American	2.92%	34

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.Tyr516=
Coding: c.1548C>T
MANE Select: NM_013280
dbSNP: rs947939
Type: single nucleotide variant
Location: chr11:64117815 (GRCh38)
Gene constraint: LOEUF 0.682 · pLI 0.14 (gnomAD)
Structure: AlphaFold pLDDT 73.46
Residue 516: 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.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
FLRT1 p.Arg592Trp 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-tyr516 (accessed [today's date]).

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