Is FLRT1 p.Pro626= (c.1878G>A) pathogenic?

FLRT1 p.Pro626= (c.1878G>A) is classified Benign/Likely benign in FLRT1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-02-01). Rare (popmax 0.294%, afr); Associated with peripheral neuropathy.

What condition is associated with FLRT1 p.Pro626= (c.1878G>A)?

FLRT1 p.Pro626= (c.1878G>A) is associated with peripheral neuropathy (ClinVar).

How common is FLRT1 p.Pro626= (c.1878G>A) in the general population?

FLRT1 p.Pro626= (c.1878G>A) is rare (popmax 0.294%, afr) (gnomAD).

FLRT1 p.Pro626=

c.1878G>A · rs143811913 · VCV1170621

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

rare (popmax 0.294%, afr)

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 -8.9	GERP -4
Overall
CADD	0.13	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.294% African / African-American · 221/75,062 alleles

Filtering AF 0.263% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.25%

Overall 0.0174% 281/1,613,832 alleles · rare exomes 155/1,461,462 · genomes 126/152,370 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.294%	340
Remaining individualsnot grpmax-eligible	0.0288%	3,472
Admixed American	0.0167%	6,003
Middle Eastern	0.0165%	6,058
East Asian	0.0111%	8,977
Ashkenazi Jewishnot grpmax-eligible	0.00676%	14,798
South Asian	0.00549%	18,216
European (non-Finnish)	0.00161%	62,104

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.Pro626=
Coding: c.1878G>A
MANE Select: NM_013280
dbSNP: rs143811913
Type: single nucleotide variant
Location: chr11:64118145 (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.Pro626Arg Uncertain significance ★ same residue
FLRT1 p.Pro626Leu 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

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-pro626 (accessed [today's date]).

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