Is FLRT1 p.Lys274= (c.822G>A) pathogenic?

FLRT1 p.Lys274= (c.822G>A) is classified Benign in FLRT1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-10-02). Common (popmax 5.87%, nfe) — too common for a highly-penetrant pathogenic allele; Associated with peripheral neuropathy.

What condition is associated with FLRT1 p.Lys274= (c.822G>A)?

FLRT1 p.Lys274= (c.822G>A) is associated with peripheral neuropathy (ClinVar).

FLRT1 p.Lys274=

Q: How common is FLRT1 p.Lys274= (c.822G>A) in the general population?

FLRT1 p.Lys274= (c.822G>A) is common (popmax 5.87%, nfe) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.822G>A · rs34856996 · VCV461805

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 5.87%, 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	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 5.8	GERP 0.51, phastCons 1
Overall
CADD	9.433	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 5.87% European (non-Finnish) · 68,933/1,175,134 alleles

Filtering AF 5.83% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.81%

Overall 5% 80,184/1,603,572 alleles · common exomes 74,034/1,451,230 · genomes 6,150/152,342 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	5.87%	17
Ashkenazi Jewishnot grpmax-eligible	5.65%	18
Amishnot grpmax-eligible	5.04%	20
Finnishnot grpmax-eligible	4.38%	23
Remaining individualsnot grpmax-eligible	4.34%	23
Middle Eastern	3.87%	26
Admixed American	2.53%	40
South Asian	1.86%	54
African / African-American	0.937%	107
East Asian	0.0136%	7,376

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.Lys274=
Coding: c.822G>A
MANE Select: NM_013280
dbSNP: rs34856996
Type: single nucleotide variant
Location: chr11:64117089 (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.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-lys274 (accessed [today's date]).

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