Is FERMT3 p.Phe549= (c.1647C>T) pathogenic?

FERMT3 p.Phe549= (c.1647C>T) is classified Likely benign in FERMT3 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-05-05). Ultra-rare (popmax 0.032%, afr); Associated with leukocyte adhesion deficiency 3.

What condition is associated with FERMT3 p.Phe549= (c.1647C>T)?

FERMT3 p.Phe549= (c.1647C>T) is associated with leukocyte adhesion deficiency 3 (ClinVar).

How common is FERMT3 p.Phe549= (c.1647C>T) in the general population?

FERMT3 p.Phe549= (c.1647C>T) is ultra-rare (popmax 0.032%, afr) (gnomAD).

How is Leukocyte adhesion deficiency inherited?

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

FERMT3 p.Phe549=

c.1647C>T · rs370038112 · VCV1595978

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.032%, afr)

Conditions

leukocyte adhesion deficiency 3

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 -13	GERP -4
Overall
CADD	1.457	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.032% African / African-American · 24/74,944 alleles

Filtering AF 0.022% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0187%

Overall 0.00199% 32/1,610,412 alleles · ultra-rare exomes 20/1,458,180 · genomes 12/152,232 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.032%	3,123
Remaining individualsnot grpmax-eligible	0.0032%	31,229
Admixed American	0.00167%	60,004
South Asian	0.0011%	91,094
European (non-Finnish)	0.000339%	294,998

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.Phe549=
Coding: c.1647C>T
MANE Select: NM_031471
dbSNP: rs370038112
Type: single nucleotide variant
Location: chr11:64221117 (GRCh38)
Gene constraint: LOEUF 0.556 · pLI 0.17 (gnomAD)
Structure: AlphaFold pLDDT 83.80 · 6 PDB
Residue 549: the ferm domain

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-phe549 (accessed [today's date]).

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