Is F13A1 p.Pro332= (c.996A>C) pathogenic?

F13A1 p.Pro332= (c.996A>C) is classified Benign in F13A1 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-05-11). Common (popmax 20.4%, nfe) — too common for a highly-penetrant pathogenic allele; Associated with factor XIII, A subunit, deficiency of.

What condition is associated with F13A1 p.Pro332= (c.996A>C)?

F13A1 p.Pro332= (c.996A>C) is associated with factor XIII, A subunit, deficiency of (ClinVar).

How is Congenital factor XIII deficiency inherited?

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

F13A1 p.Pro332=

Q: How common is F13A1 p.Pro332= (c.996A>C) in the general population?

F13A1 p.Pro332= (c.996A>C) is common (popmax 20.4%, nfe) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.996A>C · rs5981 · VCV255187

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Common

common (popmax 20.4%, nfe) — too common for a highly-penetrant pathogenic allele

Conditions

factor XIII, A subunit, deficiency of

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.077	moderately benign-leaning
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -0.88	GERP -1.3, phastCons 0.009
Overall
CADD	8.345	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 20.4% European (non-Finnish) · 241,092/1,179,756 alleles

Filtering AF 20.4% ClinGen BA1/BS1 input FAF95, joint · FAF99 20.3%

Overall 18.3% 295,861/1,613,808 alleles · common exomes 272,946/1,461,586 · genomes 22,915/152,222 · joint denominator

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	23.6%	4
European (non-Finnish)grpmax	20.4%	5
Finnishnot grpmax-eligible	18.5%	5
Ashkenazi Jewishnot grpmax-eligible	17.6%	6
Remaining individualsnot grpmax-eligible	17%	6
South Asian	13.5%	7
Admixed American	12.9%	8
Middle Eastern	11.1%	9
African / African-American	8.1%	12
East Asian	0.123%	816

Amish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: F13A1
Protein: p.Pro332=
Coding: c.996A>C
MANE Select: NM_000129
dbSNP: rs5981
Type: single nucleotide variant
Location: chr6:6222149 (GRCh38)
Gene constraint: LOEUF 0.734 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.15 · 15 PDB

Full F13A1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

factor XIII, A 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

F13A1 c.691-1G>A Pathogenic/Likely pathogenic ★★ same condition
F13A1 p.Arg327Gln Pathogenic/Likely pathogenic ★★ same condition
F13A1 p.Arg662Ter Pathogenic ★★ same condition
F13A1 p.Arg682His Pathogenic ★★ ⚠ same condition
F13A1 p.Arg78Cys Pathogenic/Likely pathogenic ★★ same condition
F13A1 p.Gly274Arg Likely pathogenic ★★ same condition
F13A1 c.*1045C>G Uncertain significance ★★ same condition
F13A1 p.Ala498Ser 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/f13a1-p-pro332 (accessed [today's date]).

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