Is RABL3 p.Phe93= (c.279C>T) pathogenic?

RABL3 p.Phe93= (c.279C>T) is classified Likely benign in RABL3 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2023-12-20). Ultra-rare (popmax 0.0166%, mid); Associated with RABL3-related disorder.

What condition is associated with RABL3 p.Phe93= (c.279C>T)?

RABL3 p.Phe93= (c.279C>T) is associated with RABL3-related disorder (ClinVar).

How common is RABL3 p.Phe93= (c.279C>T) in the general population?

RABL3 p.Phe93= (c.279C>T) is ultra-rare (popmax 0.0166%, mid) (gnomAD).

RABL3 p.Phe93=

c.279C>T · rs1708545909 · VCV3057478

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0166%, mid)

Conditions

RABL3-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.4	GERP 0.039, phastCons 1
Overall
CADD	14.52	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0166% Middle Eastern · 1/6,024 alleles

Overall 6.94e-05% 1/1,441,876 alleles · ultra-rare

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: RABL3
Protein: p.Phe93=
Coding: c.279C>T
MANE Select: NM_173825
dbSNP: rs1708545909
Type: single nucleotide variant
Location: chr3:120706104 (GRCh38)
Gene constraint: LOEUF 1.415 · pLI 0.07 (gnomAD)
Structure: AlphaFold pLDDT 81.14
Residue 93: 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

Disease context

RABL3-related disorder

Similar variants

RABL3 p.Asn127Tyr Uncertain significance ★ ⚠ same condition
RABL3 p.His153Asp Uncertain significance ★ ⚠ same condition
RABL3 p.Thr98Ile Uncertain significance ★ ⚠ same condition
RABL3 p.Val119Met Uncertain significance ★ ⚠ same condition
RABL3 c.138+1G>A Uncertain significance same condition
RABL3 c.268+6A>G Benign same condition
RABL3 c.384-3C>T Likely benign same condition
RABL3 c.646-8G>C Benign same condition

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-phe93 (accessed [today's date]).

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