Is RTCB p.Arg368Trp (c.1102C>T) pathogenic?

RTCB p.Arg368Trp (c.1102C>T) is classified Uncertain significance in RTCB (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-29). AlphaMissense: likely benign (0.3099); Very rare (popmax 0.00458%, nfe).

How common is RTCB p.Arg368Trp (c.1102C>T) in the general population?

RTCB p.Arg368Trp (c.1102C>T) is very rare (popmax 0.00458%, nfe) (gnomAD).

What do computational predictors say about RTCB p.Arg368Trp (c.1102C>T)?

AlphaMissense predicts likely benign (score 0.3099) — an in-silico prediction, not a clinical call.

RTCB p.Arg368Trp

c.1102C>T · rs1022695727 · VCV2299230

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3099 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00458%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.3099	likely benign
REVEL	0.258	benign-leaning
SaProt	LLR -14.12	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.25 · evaluated, not missing
Constraint at this position
Conservation	phyloP 4.4	GERP -0.42, phastCons 1
Regional constraint	o/e 0.85	unconstrained · MANE · 8,229 bp · p 0.0093 · regional, not allelic
Overall
CADD	28.2	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 0.00458% European (non-Finnish) · 54/1,180,032 alleles

Filtering AF 0.00358% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00321%

Overall 0.00347% 56/1,614,046 alleles · very rare exomes 54/1,461,876 · genomes 2/152,170 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00458%	21,852
Admixed American	0.00333%	29,997

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: RTCB
Protein: p.Arg368Trp
Coding: c.1102C>T
MANE Select: NM_014306
dbSNP: rs1022695727
Type: single nucleotide variant
Location: chr22:32395103 (GRCh38)
Gene constraint: LOEUF 0.622 · pLI 0.17 (gnomAD)
Structure: AlphaFold pLDDT 95.66 · 5 PDB
Residue 368: a β-strand

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

Similar variants

RTCB p.Ala276= Benign ★★ same type
RTCB p.Val347= Benign ★★ same type
RTCB p.Ala101Thr Uncertain significance ★ ⚠ same type
RTCB p.Ala211Val Uncertain significance ★ ⚠ same type
RTCB p.Ala242Ser Uncertain significance ★ ⚠ same type
RTCB p.Ala294Val Uncertain significance ★ ⚠ same type
RTCB p.Ala296Thr Uncertain significance ★ ⚠ same type
RTCB p.Ala333Ser 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/rtcb-p-arg368trp (accessed [today's date]).

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