Is RABL6 p.Arg697Pro (c.2090G>C) pathogenic?

RABL6 p.Arg697Pro (c.2090G>C) is classified Uncertain significance in RABL6 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-06). AlphaMissense: likely benign (0.0984); Ultra-rare (popmax 0.0709%, eas).

How common is RABL6 p.Arg697Pro (c.2090G>C) in the general population?

RABL6 p.Arg697Pro (c.2090G>C) is ultra-rare (popmax 0.0709%, eas) (gnomAD).

What do computational predictors say about RABL6 p.Arg697Pro (c.2090G>C)?

AlphaMissense predicts likely benign (score 0.0984) — an in-silico prediction, not a clinical call.

RABL6 p.Arg697Pro

c.2090G>C · VCV3942074

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0984 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0709%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0984	likely benign
REVEL	0.231	benign-leaning
SaProt	LLR -5.74	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 5.2	GERP -0.33, phastCons 0.98
Regional constraint	o/e 1.26	unconstrained · MANE · 2,621 bp · p 1.7e-08 · regional, not allelic
Overall
CADD	15.94	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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

Grpmax group 0.0709% East Asian · 29/40,888 alleles

Filtering AF 0.0507% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0438%

Overall 0.00187% 29/1,549,704 alleles · ultra-rare exomes 28/1,397,590 · genomes 1/152,114 · joint denominator

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: RABL6
Protein: p.Arg697Pro
Coding: c.2090G>C
MANE Select: NM_024718
Type: single nucleotide variant
Location: chr9:136840422 (GRCh38)
Gene constraint: LOEUF 0.588 · pLI 0.15 (gnomAD)
Structure: AlphaFold pLDDT 60.84
Residue 697: the 'disordered' region

Full RABL6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

RABL6 p.Arg697His Uncertain significance ★ ⚠ same residue
RABL6 p.Arg697Ser Uncertain significance ★ ⚠ same residue
RABL6 p.Arg690Gln Uncertain significance ★★ ⚠ same type
RABL6 p.Ser402Thr Uncertain significance ★★ ⚠ same type
RABL6 p.Ser535Gly Uncertain significance ★★ ⚠ same type
RABL6 p.Arg280His Benign/Likely benign ★★ same type
RABL6 p.Arg533His Benign ★★ same type
RABL6 p.Pro518Leu Benign ★★ 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/rabl6-p-arg697pro (accessed [today's date]).

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