Is F2 p.Arg560Gln (c.1679G>A) pathogenic?

F2 p.Arg560Gln (c.1679G>A) is classified Uncertain significance in F2 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-11-14). AlphaMissense: likely benign (0.1501); Very rare (popmax 0.00133%, afr).

How common is F2 p.Arg560Gln (c.1679G>A) in the general population?

F2 p.Arg560Gln (c.1679G>A) is very rare (popmax 0.00133%, afr) (gnomAD).

What do computational predictors say about F2 p.Arg560Gln (c.1679G>A)?

AlphaMissense predicts likely benign (score 0.1501) — an in-silico prediction, not a clinical call.

F2 p.Arg560Gln

c.1679G>A · rs779071898 · VCV1303191

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1501 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1501	likely benign
REVEL	0.796	moderately pathogenic-leaning
SaProt	LLR -7.23	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.5	GERP 1.2, phastCons 1
Regional constraint	o/e 0.76	unconstrained · MANE · 20 kb · p 1.8e-12 · regional, not allelic
Overall
CADD	28.0	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 0.00133% African / African-American · 1/74,926 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000434% 7/1,614,082 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0016%	62,486
African / African-Americangrpmax	0.00133%	74,926
South Asian	0.0011%	91,082
European (non-Finnish)	0.000339%	295,011

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: F2
Protein: p.Arg560Gln
Coding: c.1679G>A
MANE Select: NM_000506
dbSNP: rs779071898
Type: single nucleotide variant
Location: chr11:46739072 (GRCh38)
Gene constraint: LOEUF 0.552 · pLI 0.15 (gnomAD)
Structure: AlphaFold pLDDT 84.37 · 480 PDB
Residue 560: the peptidase s1 domain; the 'high affinity receptor-binding region which is also known as the tp508 peptide' region

Full F2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

F2 p.Arg560Ter Pathogenic ★ same residue
F2 p.Arg560= Likely benign ★ same residue
F2 p.Arg314His Likely pathogenic ★★ ⚠ same type
F2 p.Arg461Trp Pathogenic/Likely pathogenic ★★ same type
F2 p.Arg500Gln Pathogenic ★★ ⚠ same type
F2 p.Arg581Cys Pathogenic/Likely pathogenic ★★ same type
F2 p.Arg596Gln Pathogenic ★★ ⚠ same type
F2 p.Gln387Ter 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/f2-p-arg560gln (accessed [today's date]).

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