Is FLRT1 p.Ala148Gly (c.443C>G) pathogenic?

FLRT1 p.Ala148Gly (c.443C>G) is classified Uncertain significance in FLRT1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-05-17). Very rare (popmax 0.00446%, eas); Associated with peripheral neuropathy.

What condition is associated with FLRT1 p.Ala148Gly (c.443C>G)?

FLRT1 p.Ala148Gly (c.443C>G) is associated with peripheral neuropathy (ClinVar).

How common is FLRT1 p.Ala148Gly (c.443C>G) in the general population?

FLRT1 p.Ala148Gly (c.443C>G) is very rare (popmax 0.00446%, eas) (gnomAD).

FLRT1 p.Ala148Gly

c.443C>G · rs80061941 · VCV969374

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00446%, eas)

Conditions

peripheral neuropathy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.1	moderately benign-leaning
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 6	GERP 2, phastCons 1
Regional constraint	o/e 0.78	unconstrained · MANE · 2,021 bp · p 5.7e-12 · regional, not allelic
Overall
CADD	23.4	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00446% East Asian · 2/44,874 alleles

Filtering AF 0.000739% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000276%

Overall 0.000186% 3/1,613,822 alleles · very rare exomes 1/1,461,472 · genomes 2/152,350 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00446%	22,437
Remaining individualsnot grpmax-eligible	0.0016%	62,500

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.Ala148Gly
Coding: c.443C>G
MANE Select: NM_013280
dbSNP: rs80061941
Type: single nucleotide variant
Location: chr11:64116710 (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.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
FLRT1 p.Asp598Asn 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-ala148gly (accessed [today's date]).

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