Is F11 p.Leu280= (c.840A>G) pathogenic?

F11 p.Leu280= (c.840A>G) is classified Likely benign in F11 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-24). Very rare (popmax 0.00666%, amr).

How common is F11 p.Leu280= (c.840A>G) in the general population?

F11 p.Leu280= (c.840A>G) is very rare (popmax 0.00666%, amr) (gnomAD).

F11 p.Leu280=

c.840A>G · rs748788469 · VCV1142362

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00666%, amr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.008	strongly benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2.9	GERP -4.7
Overall
CADD	0.037	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00666% Admixed American · 4/60,030 alleles

Filtering AF 0.00225% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00135%

Overall 0.000274% 4/1,461,876 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.Leu280=
Coding: c.840A>G
MANE Select: NM_001322131 · reported on NM_000128
dbSNP: rs748788469
Type: single nucleotide variant
Location: chr4:186280096 (GRCh38)
Structure: AlphaFold pLDDT 68.98

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

Similar variants

ZNF160 p.Ser280Arg Uncertain significance ★ ⚠ same residue
F11 c.1136-1G>C Likely pathogenic ★★ same type
F11 c.1480+1G>T Likely pathogenic ★★ same type
F11 c.1481-1G>T Likely pathogenic ★★ same type
F11 c.1716+1G>A Pathogenic ★★ same type
F11 c.325+1G>A Pathogenic ★★ same type
F11 c.326-1G>A Pathogenic ★★ same type
F11 c.595+3A>G Pathogenic/Likely 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-leu280 (accessed [today's date]).

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