Is F13B p.Leu55fs (c.162dup) pathogenic?

F13B p.Leu55fs (c.162dup) is classified Pathogenic in F13B (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-11). Very rare (popmax 0.00223%, eas).

How common is F13B p.Leu55fs (c.162dup) in the general population?

F13B p.Leu55fs (c.162dup) is very rare (popmax 0.00223%, eas) (gnomAD).

F13B p.Leu55fs

c.162dup · rs746736072 · VCV1069026

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 2 of 12
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.42	GERP -2.8

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,846 alleles

Overall 0.000186% 3/1,613,778 alleles · very rare exomes 3/1,461,570 · genomes 0/152,208 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,846
Admixed American	0.00167%	59,978
Remaining individualsnot grpmax-eligible	0.0016%	62,486

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.Leu55fs
Coding: c.162dup
MANE Select: NM_001994
dbSNP: rs746736072
Type: Duplication
Location: chr1:197062959 (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 55: the sushi 1 domain; a β-strand

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

Similar variants

F13B p.Cys59fs Likely pathogenic ★ same type
F13B p.Lys352Ter Likely pathogenic ★ same type
F13B p.Pro386fs Pathogenic ★ 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-leu55fs (accessed [today's date]).

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