Is FERMT3 p.Ala243= (c.729C>T) pathogenic?

FERMT3 p.Ala243= (c.729C>T) is classified Benign in FERMT3 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-02-04). Common (popmax 14.4%, amr) — too common for a highly-penetrant pathogenic allele; Associated with leukocyte adhesion deficiency 3.

What condition is associated with FERMT3 p.Ala243= (c.729C>T)?

FERMT3 p.Ala243= (c.729C>T) is associated with leukocyte adhesion deficiency 3 (ClinVar).

How is Leukocyte adhesion deficiency inherited?

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

FERMT3 p.Ala243=

Q: How common is FERMT3 p.Ala243= (c.729C>T) in the general population?

FERMT3 p.Ala243= (c.729C>T) is common (popmax 14.4%, amr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.729C>T · rs17851033 · VCV1170120

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Common

common (popmax 14.4%, amr) — too common for a highly-penetrant pathogenic allele

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 -20	GERP -4
Overall
CADD	0.595	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 14.4% Admixed American · 8,634/60,006 alleles

Filtering AF 14.1% ClinGen BA1/BS1 input FAF95, joint · FAF99 14%

Overall 6.92% 111,634/1,614,078 alleles · common exomes 102,234/1,461,834 · genomes 9,400/152,244 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	14.4%	7
South Asian	12%	8
Middle Eastern	10.8%	9
Remaining individualsnot grpmax-eligible	7.08%	14
Ashkenazi Jewishnot grpmax-eligible	6.64%	15
European (non-Finnish)	6.61%	15
Finnishnot grpmax-eligible	5.11%	20
East Asian	3.73%	27
Amishnot grpmax-eligible	3.62%	28
African / African-American	2.7%	37

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.Ala243=
Coding: c.729C>T
MANE Select: NM_031471
dbSNP: rs17851033
Type: single nucleotide variant
Location: chr11:64211690 (GRCh38)
Gene constraint: LOEUF 0.556 · pLI 0.17 (gnomAD)
Structure: AlphaFold pLDDT 83.80 · 6 PDB
Residue 243: 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.Ala243Gly Uncertain significance ★ ⚠ same residue
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

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-ala243 (accessed [today's date]).

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