Is F2RL1 p.Arg2Gln (c.5G>A) pathogenic?

F2RL1 p.Arg2Gln (c.5G>A) is classified Uncertain significance in F2RL1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-01-06). AlphaMissense: likely benign (0.2223); Very rare (popmax 0.00239%, nfe).

How common is F2RL1 p.Arg2Gln (c.5G>A) in the general population?

F2RL1 p.Arg2Gln (c.5G>A) is very rare (popmax 0.00239%, nfe) (gnomAD).

What do computational predictors say about F2RL1 p.Arg2Gln (c.5G>A)?

AlphaMissense predicts likely benign (score 0.2223) — an in-silico prediction, not a clinical call.

F2RL1 p.Arg2Gln

c.5G>A · rs1391745685 · VCV2473370

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2223 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00239%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2223	likely benign
REVEL	0.153	moderately benign-leaning
SaProt	LLR -7.92	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.2	GERP 2, phastCons 0.91
Regional constraint	o/e 0.90	unconstrained · MANE · 15 kb · p 0.036 · regional, not allelic
Overall
CADD	18.31	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 0.00239% European (non-Finnish) · 28/1,173,712 alleles

Filtering AF 0.00165% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00142%

Overall 0.00177% 28/1,582,884 alleles · very rare exomes 28/1,430,584 · genomes 0/152,300 · joint denominator

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: F2RL1
Protein: p.Arg2Gln
Coding: c.5G>A
MANE Select: NM_005242
dbSNP: rs1391745685
Type: single nucleotide variant
Location: chr5:76819187 (GRCh38)
Gene constraint: LOEUF 0.989 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.92 · 7 PDB

Full F2RL1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

F2RL1 p.Arg2= Benign ★★ same residue
F2RL1 p.Ala12Val Uncertain significance ★ ⚠ same type
F2RL1 p.Ala188Thr Uncertain significance ★ ⚠ same type
F2RL1 p.Ala18Ser Uncertain significance ★ ⚠ same type
F2RL1 p.Ala220Val Uncertain significance ★ ⚠ same type
F2RL1 p.Ala273Thr Uncertain significance ★ ⚠ same type
F2RL1 p.Ala358Thr Uncertain significance ★ ⚠ same type
F2RL1 p.Arg284Lys 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/f2rl1-p-arg2gln (accessed [today's date]).

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