Is F13B p.Cys255= (c.765C>T) pathogenic?

F13B p.Cys255= (c.765C>T) is classified Conflicting classifications of pathogenicity in F13B (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-07-17). Low-frequency (popmax 2.67%, afr); Associated with factor XIII, b subunit, deficiency of.

What condition is associated with F13B p.Cys255= (c.765C>T)?

F13B p.Cys255= (c.765C>T) is associated with factor XIII, b subunit, deficiency of (ClinVar).

How common is F13B p.Cys255= (c.765C>T) in the general population?

F13B p.Cys255= (c.765C>T) is low-frequency (popmax 2.67%, afr) (gnomAD).

How is Congenital factor XIII deficiency inherited?

Typically Autosomal recessive, Not applicable (Orphanet). A genetic counselor can assess individual risk for a family.

F13B p.Cys255=

c.765C>T · rs5994 · VCV787218

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

low-frequency (popmax 2.67%, afr)

Conditions

factor XIII, b subunit, deficiency of

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 2.5	GERP -0.69, phastCons 1
Overall
CADD	7.95	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 2.67% African / African-American · 2,000/74,938 alleles

Filtering AF 2.57% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.53%

Overall 0.141% 2,276/1,612,346 alleles · low-frequency exomes 1,151/1,460,244 · genomes 1,125/152,102 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	2.67%	37
Remaining individualsnot grpmax-eligible	0.248%	403
Middle Eastern	0.165%	604
Admixed American	0.145%	689
South Asian	0.00879%	11,373
European (non-Finnish)	0.00136%	73,682

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: F13B
Protein: p.Cys255=
Coding: c.765C>T
MANE Select: NM_001994
dbSNP: rs5994
Type: single nucleotide variant
Location: chr1:197060406 (GRCh38)
Gene constraint: LOEUF 0.893 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 80.55 · 2 PDB
Residue 255: a disulfide bond; the sushi 4 domain; a β-strand

Full F13B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

factor XIII, b subunit, deficiency of — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Congenital factor XIII deficiency (Orphanet):

Inheritance: Autosomal recessive, Not applicable
Onset: All ages
Prevalence: <1 / 1 000 000 (Europe)

Similar variants

F13B c.805+1G>A Likely pathogenic ★★ same condition
F13B c.986-4T>C Uncertain significance ★★ same condition
F13B p.Ala363= Uncertain significance ★★ same condition
F13B p.Arg293Cys Uncertain significance ★★ ⚠ same condition
F13B p.Arg645Ser Uncertain significance ★★ ⚠ same condition
F13B p.His225Gln Uncertain significance ★★ ⚠ same condition
F13B p.His557Arg Uncertain significance ★★ ⚠ same condition
F13B p.Tyr354His 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/f13b-p-cys255 (accessed [today's date]).

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