Is F2 p.Arg40Gln (c.119G>A) pathogenic?

F2 p.Arg40Gln (c.119G>A) is classified Uncertain significance in F2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-18). AlphaMissense: likely benign (0.2608); Very rare (popmax 0.00175%, amr).

How common is F2 p.Arg40Gln (c.119G>A) in the general population?

F2 p.Arg40Gln (c.119G>A) is very rare (popmax 0.00175%, amr) (gnomAD).

What do computational predictors say about F2 p.Arg40Gln (c.119G>A)?

AlphaMissense predicts likely benign (score 0.2608) — an in-silico prediction, not a clinical call.

F2 p.Arg40Gln

c.119G>A · VCV4688231

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2608 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00175%, amr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2608	likely benign
REVEL	0.868	moderately pathogenic-leaning
SaProt	LLR -10.57	damaging
⇒ REVEL and SaProt call this damaging; AlphaMissense does not.
Splicing
SpliceAI	Δ0.56	acceptor gain · deltas
Pangolin	Δ0.35	gain · loss 0.04 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 12	GERP 1.8, phastCons 1
Regional constraint	o/e 0.76	unconstrained · MANE · 20 kb · p 1.8e-12 · regional, not allelic
Overall
CADD	35.0	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 0.00175% Admixed American · 1/57,146 alleles

Filtering AF 0.000619% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000477%

Overall 0.00094% 15/1,595,910 alleles · very rare exomes 15/1,443,612 · genomes 0/152,298 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00175%	57,146
South Asian	0.00114%	87,534
European (non-Finnish)	0.00111%	90,197

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.Arg40Gln
Coding: c.119G>A
MANE Select: NM_000506
Type: single nucleotide variant
Location: chr11:46719741 (GRCh38)
Gene constraint: LOEUF 0.552 · pLI 0.15 (gnomAD)
Structure: AlphaFold pLDDT 84.37 · 480 PDB

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

Similar variants

F2 p.Arg40Trp Conflicting classifications of pathogenicity ★ ⚠ 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
F2 c.559+5G>A Uncertain significance ★★ 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-arg40gln (accessed [today's date]).

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