Is F13B p.Asp409= (c.1227C>T) pathogenic?

F13B p.Asp409= (c.1227C>T) is classified Likely benign in F13B (ClinVar, No assertion criteria, 1 submitter; last evaluated 2021-09-14). Ultra-rare (popmax 0.0774%, afr); Associated with F13B-related disorder.

What condition is associated with F13B p.Asp409= (c.1227C>T)?

F13B p.Asp409= (c.1227C>T) is associated with F13B-related disorder (ClinVar).

How common is F13B p.Asp409= (c.1227C>T) in the general population?

F13B p.Asp409= (c.1227C>T) is ultra-rare (popmax 0.0774%, afr) (gnomAD).

F13B p.Asp409=

c.1227C>T · rs143489717 · VCV3051630

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0774%, afr)

Conditions

F13B-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.20	acceptor gain · deltas
Constraint at this position
Conservation	phyloP 0.14	GERP -3.7
Overall
CADD	8.16	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0774% African / African-American · 58/74,890 alleles

Filtering AF 0.0614% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0557%

Overall 0.0093% 150/1,613,220 alleles · ultra-rare exomes 105/1,461,334 · genomes 45/151,886 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0774%	1,291
Middle Eastern	0.0165%	6,052
European (non-Finnish)	0.00712%	14,044
Remaining individualsnot grpmax-eligible	0.0064%	15,619
South Asian	0.0022%	45,531
Admixed American	0.00167%	59,836

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.Asp409=
Coding: c.1227C>T
MANE Select: NM_001994
dbSNP: rs143489717
Type: single nucleotide variant
Location: chr1:197055842 (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 409: the sushi 7 domain

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

Disease context

F13B-related disorder

Similar variants

F13B p.Glu31Ter Likely pathogenic ★ same condition
F13B p.Arg293Leu Uncertain significance ⚠ same condition
F13B p.Lys352Ter Likely pathogenic ★ same condition
F13B p.Asn602Ile Uncertain significance same condition
F13B c.805+1G>A Likely pathogenic ★★ same type
F13B c.451+3A>G Uncertain significance ★★ same type
F13B c.986-4T>C Uncertain significance ★★ same type
F13B p.Ala363= Uncertain significance ★★ same type

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-asp409 (accessed [today's date]).

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