Is FLRT1 p.Asn305Lys (c.915C>A) pathogenic?

FLRT1 p.Asn305Lys (c.915C>A) is classified Uncertain significance in FLRT1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-05-23). Very rare (popmax 0.00746%, nfe); Associated with peripheral neuropathy.

What condition is associated with FLRT1 p.Asn305Lys (c.915C>A)?

FLRT1 p.Asn305Lys (c.915C>A) is associated with peripheral neuropathy (ClinVar).

How common is FLRT1 p.Asn305Lys (c.915C>A) in the general population?

FLRT1 p.Asn305Lys (c.915C>A) is very rare (popmax 0.00746%, nfe) (gnomAD).

FLRT1 p.Asn305Lys

c.915C>A · rs185115330 · VCV1025266

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00746%, nfe)

Conditions

peripheral neuropathy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.172	moderately benign-leaning
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 2.2	GERP 2, phastCons 1
Regional constraint	o/e 0.78	unconstrained · MANE · 2,021 bp · p 5.7e-12 · regional, not allelic
Overall
CADD	18.01	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00746% European (non-Finnish) · 88/1,180,026 alleles

Filtering AF 0.00615% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00573%

Overall 0.00551% 89/1,614,092 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00746%	13,409
African / African-American	0.00133%	75,070

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.Asn305Lys
Coding: c.915C>A
MANE Select: NM_013280
dbSNP: rs185115330
Type: single nucleotide variant
Location: chr11:64117182 (GRCh38)

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

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-asn305lys (accessed [today's date]).

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