Is FERMT3 p.Ser386Arg (c.1158C>G) pathogenic?

FERMT3 p.Ser386Arg (c.1158C>G) is classified Conflicting classifications of pathogenicity in FERMT3 (ClinVar, Conflicting submitters, 6 submitters; last evaluated 2026-02-10). AlphaMissense: likely pathogenic (0.5981); Rare (popmax 0.285%, afr); Associated with leukocyte adhesion deficiency 3.

What condition is associated with FERMT3 p.Ser386Arg (c.1158C>G)?

FERMT3 p.Ser386Arg (c.1158C>G) is associated with leukocyte adhesion deficiency 3 (ClinVar).

How common is FERMT3 p.Ser386Arg (c.1158C>G) in the general population?

FERMT3 p.Ser386Arg (c.1158C>G) is rare (popmax 0.285%, afr) (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.Ser386Arg (c.1158C>G)?

AlphaMissense predicts likely pathogenic (score 0.5981) — an in-silico prediction, not a clinical call.

FERMT3 p.Ser386Arg

c.1158C>G · rs75295961 · VCV537723

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 6 submitters

AlphaMissense

likely pathogenic

0.5981 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.285%, afr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

leukocyte adhesion deficiency 3

Computational evidence

Protein change
AlphaMissense	0.5981	likely pathogenic
REVEL	0.819	moderately pathogenic-leaning
SaProt	LLR -10.23	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.2	GERP -2.1, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 16 kb · p 2.9e-07 · regional, not allelic
Overall
CADD	22.3	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 S390R vs ClinVar S386R) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.285% African / African-American · 214/75,042 alleles

Filtering AF 0.254% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.242%

Overall 0.0151% 244/1,613,850 alleles · rare exomes 113/1,461,572 · genomes 131/152,278 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.285%	351
Admixed American	0.0217%	4,617
Remaining individualsnot grpmax-eligible	0.0208%	4,808
South Asian	0.0022%	45,543
European (non-Finnish)	0.000169%	590,002

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: FERMT3
Protein: p.Ser386Arg
Coding: c.1158C>G
MANE Select: NM_031471
dbSNP: rs75295961
Type: single nucleotide variant
Location: chr11:64219969 (GRCh38)
Gene constraint: LOEUF 0.556 · pLI 0.17 (gnomAD)
Structure: AlphaFold pLDDT 83.80 · 6 PDB
Residue 390 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

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-ser386arg (accessed [today's date]).

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