Is FERMT3 p.Arg103Trp (c.307C>T) pathogenic?

FERMT3 p.Arg103Trp (c.307C>T) is classified Uncertain significance in FERMT3 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-27). AlphaMissense: likely benign (0.1271); Very rare (popmax 0.00833%, amr); Associated with leukocyte adhesion deficiency 3.

What condition is associated with FERMT3 p.Arg103Trp (c.307C>T)?

FERMT3 p.Arg103Trp (c.307C>T) is associated with leukocyte adhesion deficiency 3 (ClinVar).

How common is FERMT3 p.Arg103Trp (c.307C>T) in the general population?

FERMT3 p.Arg103Trp (c.307C>T) is very rare (popmax 0.00833%, amr) (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.Arg103Trp (c.307C>T)?

AlphaMissense predicts likely benign (score 0.1271) — an in-silico prediction, not a clinical call.

FERMT3 p.Arg103Trp

c.307C>T · rs572874105 · VCV1348706

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1271 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00833%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

leukocyte adhesion deficiency 3

Computational evidence

Protein change
AlphaMissense	0.1271	likely benign
REVEL	0.056	moderately benign-leaning
SaProt	LLR -10.43	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.057	GERP -2.2, phastCons 0.88
Regional constraint	o/e 0.83	unconstrained · MANE · 16 kb · p 2.9e-07 · regional, not allelic
Overall
CADD	19.46	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00833% Admixed American · 5/60,030 alleles

Filtering AF 0.00664% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00616%

Overall 0.00657% 106/1,614,148 alleles · very rare exomes 97/1,461,834 · genomes 9/152,314 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00833%	12,006
European (non-Finnish)	0.00797%	12,553
African / African-American	0.00666%	15,007
Remaining individualsnot grpmax-eligible	0.0016%	62,512
South Asian	0.0011%	91,088

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.Arg103Trp
Coding: c.307C>T
MANE Select: NM_031471
dbSNP: rs572874105
Type: single nucleotide variant
Location: chr11:64210757 (GRCh38)
Gene constraint: LOEUF 0.556 · pLI 0.17 (gnomAD)
Structure: AlphaFold pLDDT 83.80 · 6 PDB
Residue 103: 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.Arg103Gln 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.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-arg103trp (accessed [today's date]).

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