Is RABL3 p.Ser87= (c.261C>T) pathogenic?

RABL3 p.Ser87= (c.261C>T) is classified Likely benign in RABL3 (ClinVar, Single submitter, 2 submitters; last evaluated 2025-10-01). Rare (popmax 0.684%, nfe).

How common is RABL3 p.Ser87= (c.261C>T) in the general population?

RABL3 p.Ser87= (c.261C>T) is rare (popmax 0.684%, nfe) (gnomAD).

RABL3 p.Ser87=

c.261C>T · rs35389318 · VCV2654061

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

rare (popmax 0.684%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 2.2	GERP -1.4, phastCons 1
Overall
CADD	11.43	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.684% European (non-Finnish) · 8,052/1,176,380 alleles

Filtering AF 0.672% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.667%

Overall 0.561% 9,016/1,607,196 alleles · rare exomes 8,399/1,455,096 · genomes 617/152,100 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	1.1%	91
European (non-Finnish)grpmax	0.684%	146
Remaining individualsnot grpmax-eligible	0.476%	210
Admixed American	0.221%	452
Finnishnot grpmax-eligible	0.189%	528
Middle Eastern	0.133%	754
African / African-American	0.102%	982
South Asian	0.0122%	8,194

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ser87=
Coding: c.261C>T
MANE Select: NM_173825
dbSNP: rs35389318
Type: single nucleotide variant
Location: chr3:120709787 (GRCh38)
Gene constraint: LOEUF 1.415 · pLI 0.07 (gnomAD)
Structure: AlphaFold pLDDT 81.14
Residue 87: 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); the 'switch-ii' region

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-ser87 (accessed [today's date]).

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