Is RTCB p.Met163Val (c.487A>G) pathogenic?

RTCB p.Met163Val (c.487A>G) is classified Uncertain significance in RTCB (ClinVar, Single submitter, 2 submitters; last evaluated 2025-10-24). AlphaMissense: likely benign (0.0988); Ultra-rare (popmax 0.0133%, amr).

How common is RTCB p.Met163Val (c.487A>G) in the general population?

RTCB p.Met163Val (c.487A>G) is ultra-rare (popmax 0.0133%, amr) (gnomAD).

What do computational predictors say about RTCB p.Met163Val (c.487A>G)?

AlphaMissense predicts likely benign (score 0.0988) — an in-silico prediction, not a clinical call.

RTCB p.Met163Val

c.487A>G · rs200793446 · VCV3156803

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0988 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0133%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0988	likely benign
REVEL	0.206	benign-leaning
SaProt	LLR -5.10	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 2.5, phastCons 1
Regional constraint	o/e 0.65	unconstrained · MANE · 10 kb · p 2.7e-07 · regional, not allelic
Overall
CADD	22.5	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 0.0133% Admixed American · 8/60,022 alleles

Filtering AF 0.00661% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00482%

Overall 0.00316% 51/1,613,930 alleles · ultra-rare exomes 42/1,461,610 · genomes 9/152,320 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0133%	7,503
Remaining individualsnot grpmax-eligible	0.0064%	15,622
European (non-Finnish)	0.00314%	31,888
African / African-American	0.00133%	75,036
South Asian	0.0011%	91,066

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.Met163Val
Coding: c.487A>G
MANE Select: NM_014306
dbSNP: rs200793446
Type: single nucleotide variant
Location: chr22:32401757 (GRCh38)
Gene constraint: LOEUF 0.622 · pLI 0.17 (gnomAD)
Structure: AlphaFold pLDDT 95.66 · 5 PDB

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-met163val (accessed [today's date]).

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