Is F2RL3 p.Ala231Val (c.692C>T) pathogenic?

F2RL3 p.Ala231Val (c.692C>T) is classified Likely benign in F2RL3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-14). AlphaMissense: likely benign (0.0673); Very rare (popmax 0.00111%, sas).

How common is F2RL3 p.Ala231Val (c.692C>T) in the general population?

F2RL3 p.Ala231Val (c.692C>T) is very rare (popmax 0.00111%, sas) (gnomAD).

What do computational predictors say about F2RL3 p.Ala231Val (c.692C>T)?

AlphaMissense predicts likely benign (score 0.0673) — an in-silico prediction, not a clinical call.

F2RL3 p.Ala231Val

c.692C>T · rs751518098 · VCV2602613

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0673 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00111%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0673	likely benign
REVEL	0.049	moderately benign-leaning
SaProt	LLR -1.09	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 -5.3	GERP -3.9
Regional constraint	o/e 1.02	unconstrained · MANE · 1,428 bp · p 0.56 · regional, not allelic
Overall
CADD	0.99	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 0.00111% South Asian · 1/90,384 alleles

Filtering AF 0.000616% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000474%

Overall 0.000878% 14/1,595,354 alleles · very rare exomes 13/1,443,132 · genomes 1/152,222 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00111%	90,384
European (non-Finnish)	0.0011%	90,617

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: F2RL3
Protein: p.Ala231Val
Coding: c.692C>T
MANE Select: NM_003950
dbSNP: rs751518098
Type: single nucleotide variant
Location: chr19:16890155 (GRCh38)
Gene constraint: LOEUF 1.746 · pLI 0.06 (gnomAD)
Structure: AlphaFold pLDDT 80.67 · 3 PDB

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

Similar variants

F2RL3 p.Ala231Thr Uncertain significance ★ ⚠ same residue
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

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-ala231val (accessed [today's date]).

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