Is RICTOR p.Gln272Pro (c.815A>C) pathogenic?

RICTOR p.Gln272Pro (c.815A>C) is classified Uncertain significance in RICTOR (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-20). AlphaMissense: likely benign (0.225); Ultra-rare (popmax 0.0172%, amr).

How common is RICTOR p.Gln272Pro (c.815A>C) in the general population?

RICTOR p.Gln272Pro (c.815A>C) is ultra-rare (popmax 0.0172%, amr) (gnomAD).

What do computational predictors say about RICTOR p.Gln272Pro (c.815A>C)?

AlphaMissense predicts likely benign (score 0.225) — an in-silico prediction, not a clinical call.

RICTOR p.Gln272Pro

c.815A>C · VCV3789035

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.225 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0172%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.225	likely benign
REVEL	0.285	benign-leaning
SaProt	LLR -12.35	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 2.9, phastCons 1
Regional constraint	o/e 0.66	unconstrained · MANE · 54 kb · p 8e-12 · regional, not allelic
Overall
CADD	26.2	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 0.0172% Admixed American · 10/58,096 alleles

Filtering AF 0.00927% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00701%

Overall 0.000713% 11/1,543,606 alleles · ultra-rare exomes 8/1,391,584 · genomes 3/152,022 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0172%	5,810
European (non-Finnish)	8.9e-05%	1,123,068

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.Gln272Pro
Coding: c.815A>C
MANE Select: NM_152756
Type: single nucleotide variant
Location: chr5:38978589 (GRCh38)
Gene constraint: LOEUF 0.305 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 66.57 · 16 PDB
Residue 272: 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-gln272pro (accessed [today's date]).

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