Is RICTOR p.Cys1317Ser (c.3949T>A) pathogenic?

RICTOR p.Cys1317Ser (c.3949T>A) is classified Uncertain significance in RICTOR (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-29). AlphaMissense: likely benign (0.2067); Absent from gnomAD v4.1.

How common is RICTOR p.Cys1317Ser (c.3949T>A) in the general population?

RICTOR p.Cys1317Ser (c.3949T>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about RICTOR p.Cys1317Ser (c.3949T>A)?

AlphaMissense predicts likely benign (score 0.2067) — an in-silico prediction, not a clinical call.

RICTOR p.Cys1317Ser

c.3949T>A · VCV4577955

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2067 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2067	likely benign
REVEL	0.241	benign-leaning
SaProt	LLR -3.19	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 11	GERP 1.9, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 23 kb · p 2.2e-11 · regional, not allelic
Overall
CADD	22.9	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: RICTOR
Protein: p.Cys1317Ser
Coding: c.3949T>A
MANE Select: NM_152756
Type: single nucleotide variant
Location: chr5:38949899 (GRCh38)
Gene constraint: LOEUF 0.305 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 66.57 · 16 PDB

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-cys1317ser (accessed [today's date]).

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