Is F11 p.Ser243fs (c.727dup) pathogenic?

F11 p.Ser243fs (c.727dup) is classified Pathogenic in F11 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-19). Very rare (popmax 0.00223%, eas).

How common is F11 p.Ser243fs (c.727dup) in the general population?

F11 p.Ser243fs (c.727dup) is very rare (popmax 0.00223%, eas) (gnomAD).

F11 p.Ser243fs

c.727dup · rs2477280027 · VCV2580632

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 7 of 15
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.7	GERP 2.4, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,870 alleles

Overall 6.84e-05% 1/1,461,878 alleles · very rare

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: F11
Protein: p.Ser243fs
Coding: c.727dup
MANE Select: NM_000128
dbSNP: rs2477280027
Type: Duplication
Location: chr4:186276358 (GRCh38)
Gene constraint: LOEUF 1.145 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.94 · 117 PDB
Residue 243: a disulfide bond; the apple 3 domain

Full F11 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

F11 p.Ser243Phe Pathogenic/Likely pathogenic ★★ ⚠ same residue
F11 p.Cys103Ter Pathogenic/Likely pathogenic ★★ same type
F11 p.Thr428fs Pathogenic ★★ same type
F11 p.Tyr52Ter Likely pathogenic ★★ same type
F11 p.Asp457fs Pathogenic ★ same type
F11 p.Ile164fs Likely pathogenic ★ same type
F11 p.Thr240fs Pathogenic ★ same type
F11 p.Trp73fs 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/f11-p-ser243fs (accessed [today's date]).

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