Is RABL6 p.Pro201Ser (c.601C>T) pathogenic?

RABL6 p.Pro201Ser (c.601C>T) is classified Uncertain significance in RABL6 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-25). AlphaMissense: likely benign (0.2018); Very rare (popmax 0.00223%, eas).

How common is RABL6 p.Pro201Ser (c.601C>T) in the general population?

RABL6 p.Pro201Ser (c.601C>T) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about RABL6 p.Pro201Ser (c.601C>T)?

AlphaMissense predicts likely benign (score 0.2018) — an in-silico prediction, not a clinical call.

RABL6 p.Pro201Ser

c.601C>T · VCV3429382

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2018 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.2018	likely benign
REVEL	0.427	indeterminate
SaProt	LLR -8.09	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.4	GERP 1.1, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 30 kb · p 1e-05 · regional, not allelic
Overall
CADD	24.7	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 0.00223% East Asian · 1/44,888 alleles

Overall 0.000124% 2/1,613,346 alleles · very rare exomes 2/1,461,070 · genomes 0/152,276 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,888
European (non-Finnish)	8.48e-05%	1,179,377

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.Pro201Ser
Coding: c.601C>T
MANE Select: NM_024718
Type: single nucleotide variant
Location: chr9:136832266 (GRCh38)
Gene constraint: LOEUF 0.588 · pLI 0.15 (gnomAD)
Structure: AlphaFold pLDDT 60.84
Residue 201: the 'small gtpase-like' region

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

Similar variants

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
RABL6 p.Pro539= Benign ★★ same type
RABL6 p.Pro557= Benign/Likely 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-pro201ser (accessed [today's date]).

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