Is FLRT1 p.Pro76= (c.228C>T) pathogenic?

FLRT1 p.Pro76= (c.228C>T) is classified Likely benign in FLRT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-04-10). Rare (popmax 0.66%, mid); Associated with peripheral neuropathy.

What condition is associated with FLRT1 p.Pro76= (c.228C>T)?

FLRT1 p.Pro76= (c.228C>T) is associated with peripheral neuropathy (ClinVar).

How common is FLRT1 p.Pro76= (c.228C>T) in the general population?

FLRT1 p.Pro76= (c.228C>T) is rare (popmax 0.66%, mid) (gnomAD).

FLRT1 p.Pro76=

c.228C>T · rs200049740 · VCV1107240

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.66%, mid)

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 -5.2	GERP -4
Overall
CADD	6.137	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.66% Middle Eastern · 40/6,062 alleles

Filtering AF 0.498% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.442%

Overall 0.0238% 384/1,613,980 alleles · rare exomes 343/1,461,654 · genomes 41/152,326 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.66%	152
Remaining individualsnot grpmax-eligible	0.064%	1,562
Admixed American	0.0317%	3,159
European (non-Finnish)	0.0214%	4,682
South Asian	0.0187%	5,358
Ashkenazi Jewishnot grpmax-eligible	0.0169%	5,920
African / African-American	0.0107%	9,381
Finnishnot grpmax-eligible	0.00469%	21,305

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.Pro76=
Coding: c.228C>T
MANE Select: NM_013280
dbSNP: rs200049740
Type: single nucleotide variant
Location: chr11:64116495 (GRCh38)
Gene constraint: LOEUF 0.682 · pLI 0.14 (gnomAD)
Structure: AlphaFold pLDDT 73.46
Residue 76: the lrrnt domain

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-pro76 (accessed [today's date]).

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