Is RABL3 p.Phe200Ser (c.599T>C) pathogenic?

RABL3 p.Phe200Ser (c.599T>C) is classified Uncertain significance in RABL3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-04). AlphaMissense: likely pathogenic (0.9848); Absent from gnomAD v4.1.

How common is RABL3 p.Phe200Ser (c.599T>C) in the general population?

RABL3 p.Phe200Ser (c.599T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about RABL3 p.Phe200Ser (c.599T>C)?

AlphaMissense predicts likely pathogenic (score 0.9848) — an in-silico prediction, not a clinical call.

RABL3 p.Phe200Ser

c.599T>C · rs2472842395 · VCV2616387

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9848 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9848	likely pathogenic · top 9% in RABL3
REVEL	0.899	moderately pathogenic-leaning
SaProt	LLR -13.45	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.5, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 53 kb · p 0.32 · regional, not allelic
Overall
CADD	28.8	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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: RABL3
Protein: p.Phe200Ser
Coding: c.599T>C
MANE Select: NM_173825
dbSNP: rs2472842395
Type: single nucleotide variant
Location: chr3:120694160 (GRCh38)
Gene constraint: LOEUF 1.415 · pLI 0.07 (gnomAD)
Structure: AlphaFold pLDDT 81.14
Residue 200: the 'small gtpase-like' region; a UniProt-annotated variant site (in pnca5; associated with disease susceptibility; increased kras signaling and cell proliferation; increased interaction with rap1gds1; increased kras prenylation)

Full RABL3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

RABL3 p.His95= Likely benign ★★ same type
RABL3 p.Arg222Gly Uncertain significance ★ same type
RABL3 p.Asn127Tyr Uncertain significance ★ ⚠ same type
RABL3 p.Asn172Ser Uncertain significance ★ ⚠ same type
RABL3 p.Asn192Lys Uncertain significance ★ ⚠ same type
RABL3 p.Cys180Gly Uncertain significance ★ ⚠ same type
RABL3 p.Cys27Phe Uncertain significance ★ ⚠ same type
RABL3 p.Gly128Glu 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/rabl3-p-phe200ser (accessed [today's date]).

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