Is RICTOR p.Arg6Cys (c.16C>T) pathogenic?

RICTOR p.Arg6Cys (c.16C>T) is classified Uncertain significance in RICTOR (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-01). AlphaMissense: likely pathogenic (0.7176); Very rare (popmax 0.00035%, nfe).

How common is RICTOR p.Arg6Cys (c.16C>T) in the general population?

RICTOR p.Arg6Cys (c.16C>T) is very rare (popmax 0.00035%, nfe) (gnomAD).

What do computational predictors say about RICTOR p.Arg6Cys (c.16C>T)?

AlphaMissense predicts likely pathogenic (score 0.7176) — an in-silico prediction, not a clinical call.

RICTOR p.Arg6Cys

c.16C>T · VCV3945699

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7176 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00035%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.7176	likely pathogenic
REVEL	0.217	benign-leaning
SaProt	LLR -9.15	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.9, phastCons 1
Regional constraint	o/e 1.23	unconstrained · MANE · 53 kb · p 0.086 · regional, not allelic
Overall
CADD	27.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00035% European (non-Finnish) · 4/1,141,980 alleles

Filtering AF 8.2e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.5e-05%

Overall 0.00026% 4/1,538,392 alleles · very rare exomes 3/1,386,544 · genomes 1/151,848 · 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: RICTOR
Protein: p.Arg6Cys
Coding: c.16C>T
MANE Select: NM_152756
Type: single nucleotide variant
Location: chr5:39074362 (GRCh38)
Gene constraint: LOEUF 0.305 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 66.57 · 16 PDB
Residue 6: the 'interaction with nbn' region

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

Similar variants

RICTOR p.Asn749= Benign ★★ same type
RICTOR p.Ile811= Benign ★★ same type
RICTOR p.His442Arg Likely pathogenic ★ ⚠ same type
RICTOR p.Ala1350Thr Uncertain significance ★ ⚠ same type
RICTOR p.Ala146Thr Uncertain significance ★ ⚠ same type
RICTOR p.Ala246Val Uncertain significance ★ ⚠ same type
RICTOR p.Ala472Thr Uncertain significance ★ ⚠ same type
RICTOR p.Ala91Thr 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/rictor-p-arg6cys (accessed [today's date]).

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