Is FERMT3 p.Leu366Val (c.1096C>G) pathogenic?

FERMT3 p.Leu366Val (c.1096C>G) is classified Uncertain significance in FERMT3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-22). AlphaMissense: likely benign (0.2142); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with FERMT3 p.Leu366Val (c.1096C>G)?

FERMT3 p.Leu366Val (c.1096C>G) is associated with Inborn genetic diseases (ClinVar).

How common is FERMT3 p.Leu366Val (c.1096C>G) in the general population?

FERMT3 p.Leu366Val (c.1096C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about FERMT3 p.Leu366Val (c.1096C>G)?

AlphaMissense predicts likely benign (score 0.2142) — an in-silico prediction, not a clinical call.

FERMT3 p.Leu366Val

c.1096C>G · rs1946638712 · VCV3094469

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2142 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2142	likely benign
REVEL	0.733	pathogenic-leaning
SaProt	LLR -7.63	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.78	GERP -1.7, phastCons 0.9
Regional constraint	o/e 0.83	unconstrained · MANE · 16 kb · p 2.9e-07 · regional, not allelic
Overall
CADD	21.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM L370V vs ClinVar L366V) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: FERMT3
Protein: p.Leu366Val
Coding: c.1096C>G
MANE Select: NM_031471
dbSNP: rs1946638712
Type: single nucleotide variant
Location: chr11:64219907 (GRCh38)
Gene constraint: LOEUF 0.556 · pLI 0.17 (gnomAD)
Structure: AlphaFold pLDDT 83.80 · 6 PDB
Residue 370 UniProt numbering: the ferm domain; the ph domain; a β-strand

Full FERMT3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

FERMT3 p.Ala570Thr Uncertain significance ★★ ⚠ same condition
FERMT3 p.Arg200Gln Uncertain significance ★★ ⚠ same condition
FERMT3 p.Arg212His Uncertain significance ★★ ⚠ same condition
FERMT3 p.Arg234Trp Uncertain significance ★★ same condition
FERMT3 p.Arg538Cys Uncertain significance ★★ ⚠ same condition
FERMT3 p.Arg573Gln Uncertain significance ★★ ⚠ same condition
FERMT3 p.Arg603Gln Uncertain significance ★★ ⚠ same condition
FERMT3 p.Asp206Asn 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/fermt3-p-leu366val (accessed [today's date]).

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