Is F2RL3 p.Ser369Pro (c.1105T>C) pathogenic?

F2RL3 p.Ser369Pro (c.1105T>C) is classified Uncertain significance in F2RL3 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-14). AlphaMissense: likely benign (0.0769); Absent from gnomAD v4.1.

How common is F2RL3 p.Ser369Pro (c.1105T>C) in the general population?

F2RL3 p.Ser369Pro (c.1105T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about F2RL3 p.Ser369Pro (c.1105T>C)?

AlphaMissense predicts likely benign (score 0.0769) — an in-silico prediction, not a clinical call.

F2RL3 p.Ser369Pro

c.1105T>C · rs2512643371 · VCV2312040

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0769 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0769	likely benign
REVEL	0.135	moderately benign-leaning
SaProt	LLR -6.51	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 1.9	GERP -1.2, phastCons 0.033
Regional constraint	o/e 1.02	unconstrained · MANE · 1,428 bp · p 0.56 · regional, not allelic
Overall
CADD	21.2	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: F2RL3
Protein: p.Ser369Pro
Coding: c.1105T>C
MANE Select: NM_003950
dbSNP: rs2512643371
Type: single nucleotide variant
Location: chr19:16890568 (GRCh38)
Gene constraint: LOEUF 1.746 · pLI 0.06 (gnomAD)
Structure: AlphaFold pLDDT 80.67 · 3 PDB
Residue 369: the 'disordered' region

Full F2RL3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

F2RL3 p.Ala120Thr Benign ★★ same type
F2RL3 p.Leu257= Benign ★★ same type
F2RL3 p.Tyr322= Benign ★★ same type
F2RL3 p.Ala128Val Uncertain significance ★ ⚠ same type
F2RL3 p.Ala186Gly Uncertain significance ★ ⚠ same type
F2RL3 p.Ala199Ser Uncertain significance ★ ⚠ same type
F2RL3 p.Ala200Val Uncertain significance ★ ⚠ same type
F2RL3 p.Ala208Ser 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/f2rl3-p-ser369pro (accessed [today's date]).

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