Is FERMT3 p.Pro203Ser (c.607C>T) pathogenic?

FERMT3 p.Pro203Ser (c.607C>T) is classified Conflicting classifications of pathogenicity in FERMT3 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2026-04-09). AlphaMissense: likely benign (0.0871); Rare (popmax 0.254%, afr); Associated with leukocyte adhesion deficiency 3.

What condition is associated with FERMT3 p.Pro203Ser (c.607C>T)?

FERMT3 p.Pro203Ser (c.607C>T) is associated with leukocyte adhesion deficiency 3 (ClinVar).

How common is FERMT3 p.Pro203Ser (c.607C>T) in the general population?

FERMT3 p.Pro203Ser (c.607C>T) is rare (popmax 0.254%, 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.Pro203Ser (c.607C>T)?

AlphaMissense predicts likely benign (score 0.0871) — an in-silico prediction, not a clinical call.

FERMT3 p.Pro203Ser

c.607C>T · rs143873934 · VCV537727

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.0871 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.254%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

leukocyte adhesion deficiency 3

Computational evidence

Protein change
AlphaMissense	0.0871	likely benign
REVEL	0.11	moderately benign-leaning
SaProt	LLR -7.34	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.7	GERP 1.1, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 16 kb · p 2.9e-07 · regional, not allelic
Overall
CADD	20.6	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 0.254% African / African-American · 190/74,922 alleles

Filtering AF 0.224% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.213%

Overall 0.0142% 229/1,610,400 alleles · rare exomes 107/1,458,218 · genomes 122/152,182 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.254%	394
Admixed American	0.0435%	2,300
Remaining individualsnot grpmax-eligible	0.0176%	5,668
European (non-Finnish)	0.00017%	589,491

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.Pro203Ser
Coding: c.607C>T
MANE Select: NM_031471
dbSNP: rs143873934
Type: single nucleotide variant
Location: chr11:64211367 (GRCh38)
Gene constraint: LOEUF 0.556 · pLI 0.17 (gnomAD)
Structure: AlphaFold pLDDT 83.80 · 6 PDB
Residue 203: 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.Pro203Leu Uncertain significance ★★ ⚠ same residue
FERMT3 p.Pro203= Likely benign ★ 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

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-pro203ser (accessed [today's date]).

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