Is F2RL1 p.Ser65Phe (c.194C>T) pathogenic?

F2RL1 p.Ser65Phe (c.194C>T) is classified Uncertain significance in F2RL1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-05). AlphaMissense: ambiguous (0.4779); Absent from gnomAD v4.1.

How common is F2RL1 p.Ser65Phe (c.194C>T) in the general population?

F2RL1 p.Ser65Phe (c.194C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about F2RL1 p.Ser65Phe (c.194C>T)?

AlphaMissense predicts ambiguous (score 0.4779) — an in-silico prediction, not a clinical call.

F2RL1 p.Ser65Phe

c.194C>T · VCV3511259

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4779 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
AlphaMissense	0.4779	ambiguous
REVEL	0.342	indeterminate
SaProt	—	withheld · numbering disagrees past residue 30 · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 15 kb · p 0.036 · regional, not allelic
Overall
CADD	24.5	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

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: F2RL1
Protein: p.Ser65Phe
Coding: c.194C>T
MANE Select: NM_005242
Type: single nucleotide variant
Location: chr5:76832801 (GRCh38)
Gene constraint: LOEUF 0.989 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.92 · 7 PDB
Residue 65: an α-helix

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

Similar variants

F2RL1 p.Arg2= Benign ★★ same type
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-ser65phe (accessed [today's date]).

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