Is F11 p.His9Arg (c.26A>G) pathogenic?

F11 p.His9Arg (c.26A>G) is classified Uncertain significance in F11 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2024-02-15). AlphaMissense: likely benign (0.0879); Very rare (popmax 0.00667%, amr); Associated with F11-related disorder.

What condition is associated with F11 p.His9Arg (c.26A>G)?

F11 p.His9Arg (c.26A>G) is associated with F11-related disorder (ClinVar).

How common is F11 p.His9Arg (c.26A>G) in the general population?

F11 p.His9Arg (c.26A>G) is very rare (popmax 0.00667%, amr) (gnomAD).

What do computational predictors say about F11 p.His9Arg (c.26A>G)?

AlphaMissense predicts likely benign (score 0.0879) — an in-silico prediction, not a clinical call.

F11 p.His9Arg

c.26A>G · rs774676239 · VCV3049951

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0879 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00667%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

F11-related disorder

Computational evidence

Protein change
AlphaMissense	0.0879	likely benign
REVEL	0.215	benign-leaning
SaProt	LLR -7.28	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.34	donor gain · deltas
Constraint at this position
Conservation	phyloP 1.6	GERP -2, phastCons 0.52
Overall
CADD	15.55	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00667% Admixed American · 4/59,976 alleles

Filtering AF 0.00226% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00135%

Overall 0.00028% 4/1,429,976 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.His9Arg
Coding: c.26A>G
MANE Select: NM_001322131 · reported on NM_000128
dbSNP: rs774676239
Type: single nucleotide variant
Location: chr4:186267162 (GRCh38)
Structure: AlphaFold pLDDT 68.98
Residue 9: the krab domain

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

Disease context

F11-related disorder

Similar variants

F11 c.1136-1G>C Likely pathogenic ★★ same condition
F11 c.1481-1G>T Likely pathogenic ★★ same condition
F11 c.1716+1G>A Pathogenic ★★ same condition
F11 c.325+1G>A Pathogenic ★★ same condition
F11 c.326-1G>A Pathogenic ★★ same condition
F11 c.595+3A>G Pathogenic/Likely pathogenic ★★ same condition
F11 c.755+2T>C Pathogenic ★★ same condition
F11 p.Ala109Thr Pathogenic ★★ ⚠ 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/f11-p-his9arg (accessed [today's date]).

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