Is F13B p.Ser419= (c.1257C>A) pathogenic?

F13B p.Ser419= (c.1257C>A) is classified Uncertain significance in F13B (ClinVar, Single submitter, 1 submitter; last evaluated 2018-03-16). Ultra-rare (popmax 0.0769%, amr); Associated with factor XIII, b subunit, deficiency of.

What condition is associated with F13B p.Ser419= (c.1257C>A)?

F13B p.Ser419= (c.1257C>A) is associated with factor XIII, b subunit, deficiency of (ClinVar).

How common is F13B p.Ser419= (c.1257C>A) in the general population?

F13B p.Ser419= (c.1257C>A) is ultra-rare (popmax 0.0769%, amr) (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.Ser419=

c.1257C>A · rs761403510 · VCV876611

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0769%, amr)

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	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.03	GERP -1.7, phastCons 0.4
Overall
CADD	0.597	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0769% Admixed American · 46/59,850 alleles

Filtering AF 0.0592% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0529%

Overall 0.00657% 106/1,613,356 alleles · ultra-rare exomes 76/1,461,458 · genomes 30/151,898 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0769%	1,301
Remaining individualsnot grpmax-eligible	0.0256%	3,904
Middle Eastern	0.0165%	6,078
European (non-Finnish)	0.00356%	28,090
African / African-American	0.00134%	74,808

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.Ser419=
Coding: c.1257C>A
MANE Select: NM_001994
dbSNP: rs761403510
Type: single nucleotide variant
Location: chr1:197055812 (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 419: the sushi 7 domain

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-ser419 (accessed [today's date]).

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