Is RICTOR p.Ile211Val (c.631A>G) pathogenic?

RICTOR p.Ile211Val (c.631A>G) is classified Uncertain significance in RICTOR (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-04). AlphaMissense: likely benign (0.1068); Ultra-rare (popmax 0.029%, eas).

How common is RICTOR p.Ile211Val (c.631A>G) in the general population?

RICTOR p.Ile211Val (c.631A>G) is ultra-rare (popmax 0.029%, eas) (gnomAD).

What do computational predictors say about RICTOR p.Ile211Val (c.631A>G)?

AlphaMissense predicts likely benign (score 0.1068) — an in-silico prediction, not a clinical call.

RICTOR p.Ile211Val

c.631A>G · VCV4154214

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1068 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.029%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.1068	likely benign
REVEL	0.397	indeterminate
SaProt	LLR -8.12	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 7.8	GERP 2.7, phastCons 1
Regional constraint	o/e 0.66	unconstrained · MANE · 54 kb · p 8e-12 · regional, not allelic
Overall
CADD	25.0	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 0.029% East Asian · 13/44,850 alleles

Filtering AF 0.0171% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0136%

Overall 0.00105% 17/1,613,314 alleles · ultra-rare exomes 14/1,461,128 · genomes 3/152,186 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.029%	3,450
African / African-American	0.00401%	24,967
South Asian	0.0011%	91,068

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.Ile211Val
Coding: c.631A>G
MANE Select: NM_152756
Type: single nucleotide variant
Location: chr5:38981989 (GRCh38)
Gene constraint: LOEUF 0.305 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 66.57 · 16 PDB
Residue 211: the 'interaction with nbn' region; an α-helix

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-ile211val (accessed [today's date]).

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