Is F13A1 p.Val415Phe (c.1243G>T) pathogenic?

F13A1 p.Val415Phe (c.1243G>T) is classified Pathogenic in F13A1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 1999-01-01). AlphaMissense: likely pathogenic (0.8328); Very rare (popmax 6.2e-05%); Associated with factor XIII, A subunit, deficiency of.

What condition is associated with F13A1 p.Val415Phe (c.1243G>T)?

F13A1 p.Val415Phe (c.1243G>T) is associated with factor XIII, A subunit, deficiency of (ClinVar).

How common is F13A1 p.Val415Phe (c.1243G>T) in the general population?

F13A1 p.Val415Phe (c.1243G>T) is very rare (popmax 6.2e-05%) (gnomAD).

How is Congenital factor XIII deficiency inherited?

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

What do computational predictors say about F13A1 p.Val415Phe (c.1243G>T)?

AlphaMissense predicts likely pathogenic (score 0.8328) — an in-silico prediction, not a clinical call.

F13A1 p.Val415Phe

c.1243G>T · rs121913070 · VCV16530

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8328 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 6.2e-05%)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

factor XIII, A subunit, deficiency of

Computational evidence

Protein change
AlphaMissense	0.8328	likely pathogenic ✓ concordant with ClinVar
REVEL	0.634	indeterminate
SaProt	LLR -13.15	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 5.9	GERP 2.4, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 173 kb · p 0.0002 · regional, not allelic
Overall
CADD	26.4	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 6.2e-05%

Overall 6.2e-05% 1/1,614,140 alleles · very rare exomes 1/1,461,872 · genomes 0/152,268 · joint denominator

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.Val415Phe
Coding: c.1243G>T
MANE Select: NM_000129
dbSNP: rs121913070
Type: single nucleotide variant
Location: chr6:6195859 (GRCh38)
Gene constraint: LOEUF 0.734 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.15 · 15 PDB
Residue 415: an α-helix

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-val415phe (accessed [today's date]).

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