Is F11 p.Arg72Pro (c.215G>C) pathogenic?

F11 p.Arg72Pro (c.215G>C) is classified Uncertain significance in F11 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-02-18). AlphaMissense: likely benign (0.2353); Very rare (popmax 0.000254%, nfe).

How common is F11 p.Arg72Pro (c.215G>C) in the general population?

F11 p.Arg72Pro (c.215G>C) is very rare (popmax 0.000254%, nfe) (gnomAD).

What do computational predictors say about F11 p.Arg72Pro (c.215G>C)?

AlphaMissense predicts likely benign (score 0.2353) — an in-silico prediction, not a clinical call.

F11 p.Arg72Pro

c.215G>C · VCV4848246

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2353 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000254%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.2353	likely benign
REVEL	0.552	indeterminate
SaProt	LLR -13.25	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.4	GERP -4.8, phastCons 0.003
Overall
CADD	14.49	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000254% European (non-Finnish) · 3/1,180,014 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000186% 3/1,614,006 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.Arg72Pro
Coding: c.215G>C
MANE Select: NM_000128
Type: single nucleotide variant
Location: chr4:186271768 (GRCh38)
Gene constraint: LOEUF 1.145 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.94 · 117 PDB
Residue 72: an α-helix; a disulfide bond; the apple 1 domain

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

Similar variants

F11 p.Arg72Ter Pathogenic ★★ 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-arg72pro (accessed [today's date]).

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