Is FLRT1 p.Ala77Thr (c.229G>A) pathogenic?

FLRT1 p.Ala77Thr (c.229G>A) is classified Uncertain significance in FLRT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2017-09-30). Very rare (popmax 0.00223%, eas); Associated with peripheral neuropathy.

What condition is associated with FLRT1 p.Ala77Thr (c.229G>A)?

FLRT1 p.Ala77Thr (c.229G>A) is associated with peripheral neuropathy (ClinVar).

How common is FLRT1 p.Ala77Thr (c.229G>A) in the general population?

FLRT1 p.Ala77Thr (c.229G>A) is very rare (popmax 0.00223%, eas) (gnomAD).

FLRT1 p.Ala77Thr

c.229G>A · rs770193280 · VCV530937

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Conditions

peripheral neuropathy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.225	benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.73	GERP -4
Regional constraint	o/e 0.78	unconstrained · MANE · 2,021 bp · p 5.7e-12 · regional, not allelic
Overall
CADD	0.028	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,868 alleles

Filtering AF 0.000365% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000137%

Overall 0.000744% 12/1,613,828 alleles · very rare exomes 12/1,461,582 · genomes 0/152,246 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.0047%	21,280
East Asiangrpmax	0.00223%	44,868
South Asian	0.0022%	45,537
Admixed American	0.00167%	60,006
European (non-Finnish)	0.000424%	235,987

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.Ala77Thr
Coding: c.229G>A
MANE Select: NM_013280
dbSNP: rs770193280
Type: single nucleotide variant
Location: chr11:64116496 (GRCh38)
Gene constraint: LOEUF 0.682 · pLI 0.14 (gnomAD)
Structure: AlphaFold pLDDT 73.46
Residue 77: 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-ala77thr (accessed [today's date]).

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