Is FLRT1 p.Ser254= (c.762G>A) pathogenic?

FLRT1 p.Ser254= (c.762G>A) is classified Likely benign in FLRT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-06-21). Very rare (popmax 0.00984%, nfe); Associated with peripheral neuropathy.

What condition is associated with FLRT1 p.Ser254= (c.762G>A)?

FLRT1 p.Ser254= (c.762G>A) is associated with peripheral neuropathy (ClinVar).

How common is FLRT1 p.Ser254= (c.762G>A) in the general population?

FLRT1 p.Ser254= (c.762G>A) is very rare (popmax 0.00984%, nfe) (gnomAD).

FLRT1 p.Ser254=

c.762G>A · rs146150625 · VCV1131761

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00984%, nfe)

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 -5.5	GERP -4
Overall
CADD	5.798	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00984% European (non-Finnish) · 116/1,179,066 alleles

Filtering AF 0.00835% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00777%

Overall 0.00739% 119/1,610,978 alleles · very rare exomes 116/1,458,894 · genomes 3/152,084 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00984%	10,164
African / African-American	0.00401%	24,937

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.Ser254=
Coding: c.762G>A
MANE Select: NM_013280
dbSNP: rs146150625
Type: single nucleotide variant
Location: chr11:64117029 (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-ser254 (accessed [today's date]).

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