Is FLRT1 p.Glu631= (c.1893A>G) pathogenic?

FLRT1 p.Glu631= (c.1893A>G) is classified Benign in FLRT1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-19). Common (popmax 100%, eas) — too common for a highly-penetrant pathogenic allele; Associated with peripheral neuropathy.

What condition is associated with FLRT1 p.Glu631= (c.1893A>G)?

FLRT1 p.Glu631= (c.1893A>G) is associated with peripheral neuropathy (ClinVar).

FLRT1 p.Glu631=

Q: How common is FLRT1 p.Glu631= (c.1893A>G) in the general population?

FLRT1 p.Glu631= (c.1893A>G) is common (popmax 100%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1893A>G · rs4379854 · VCV1166778

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 100%, eas) — 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 3	GERP -3.1, phastCons 1
Overall
CADD	4.47	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 100% East Asian · 44,889/44,890 alleles

Filtering AF 99.8% ClinGen BA1/BS1 input FAF95, joint · FAF99 99.8%

Overall 99.2% 1,601,383/1,613,808 alleles · common exomes 1,455,407/1,461,444 · genomes 145,976/152,364 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	100%	1
Ashkenazi Jewishnot grpmax-eligible	100%	1
Amishnot grpmax-eligible	100%	1
East Asiangrpmax	100%	1
European (non-Finnish)	100%	1
South Asian	100%	1
Middle Eastern	99.6%	1
Admixed American	99.1%	1
Remaining individualsnot grpmax-eligible	99%	1
African / African-American	85.1%	1

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Glu631=
Coding: c.1893A>G
MANE Select: NM_013280
dbSNP: rs4379854
Type: single nucleotide variant
Location: chr11:64118160 (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-glu631 (accessed [today's date]).

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