Is FERMT3 p.Leu652Phe (c.1954C>T) pathogenic?

FERMT3 p.Leu652Phe (c.1954C>T) is classified Uncertain significance in FERMT3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-08). AlphaMissense: ambiguous (0.4121); Absent from gnomAD v4.1; Associated with leukocyte adhesion deficiency 3.

What condition is associated with FERMT3 p.Leu652Phe (c.1954C>T)?

FERMT3 p.Leu652Phe (c.1954C>T) is associated with leukocyte adhesion deficiency 3 (ClinVar).

How common is FERMT3 p.Leu652Phe (c.1954C>T) in the general population?

FERMT3 p.Leu652Phe (c.1954C>T) is absent from gnomAD v4.1 (gnomAD).

How is Leukocyte adhesion deficiency inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about FERMT3 p.Leu652Phe (c.1954C>T)?

AlphaMissense predicts ambiguous (score 0.4121) — an in-silico prediction, not a clinical call.

FERMT3 p.Leu652Phe

c.1954C>T · rs1457484861 · VCV2716987

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4121 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

leukocyte adhesion deficiency 3

Computational evidence

Protein change
AlphaMissense	0.4121	ambiguous
REVEL	0.307	indeterminate
SaProt	LLR -9.80	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.9	GERP 0.67, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 16 kb · p 2.9e-07 · regional, not allelic
Overall
CADD	24.4	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 L656F vs ClinVar L652F) — 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.Leu652Phe
Coding: c.1954C>T
MANE Select: NM_031471
dbSNP: rs1457484861
Type: single nucleotide variant
Location: chr11:64223454 (GRCh38)
Gene constraint: LOEUF 0.556 · pLI 0.17 (gnomAD)
Structure: AlphaFold pLDDT 83.80 · 6 PDB
Residue 656 UniProt numbering: an α-helix

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

Disease context

leukocyte adhesion deficiency 3 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Leukocyte adhesion deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood, Infancy

Similar variants

FERMT3 p.Arg573Ter Pathogenic/Likely pathogenic ★★ same condition
FERMT3 p.Ala109Thr Uncertain significance ★★ ⚠ same condition
FERMT3 p.Ala338Val Uncertain significance ★★ ⚠ same condition
FERMT3 p.Ala570Thr Uncertain significance ★★ ⚠ same condition
FERMT3 p.Arg103Gln Uncertain significance ★★ ⚠ same condition
FERMT3 p.Arg111His Uncertain significance ★★ ⚠ same condition
FERMT3 p.Arg129His Uncertain significance ★★ ⚠ same condition
FERMT3 p.Arg179Leu 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-leu652phe (accessed [today's date]).

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