Is RTCB p.Asn16Ser (c.47A>G) pathogenic?

RTCB p.Asn16Ser (c.47A>G) is classified Likely benign in RTCB (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-08). AlphaMissense: likely benign (0.0558); Very rare (popmax 0.004%, afr).

How common is RTCB p.Asn16Ser (c.47A>G) in the general population?

RTCB p.Asn16Ser (c.47A>G) is very rare (popmax 0.004%, afr) (gnomAD).

What do computational predictors say about RTCB p.Asn16Ser (c.47A>G)?

AlphaMissense predicts likely benign (score 0.0558) — an in-silico prediction, not a clinical call.

RTCB p.Asn16Ser

c.47A>G · VCV4580036

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0558 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.004%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0558	likely benign
REVEL	0.06	moderately benign-leaning
SaProt	LLR -6.83	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 -0.45	GERP -5, phastCons 0.016
Regional constraint	o/e 1.03	unconstrained · MANE · 5,472 bp · p 0.72 · regional, not allelic
Overall
CADD	12.94	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 0.004% African / African-American · 3/74,908 alleles

Filtering AF 0.002% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00176%

Overall 0.0023% 37/1,609,854 alleles · very rare exomes 37/1,457,480 · genomes 0/152,374 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.004%	24,969
European (non-Finnish)	0.0028%	35,724
South Asian	0.00111%	90,366

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.Asn16Ser
Coding: c.47A>G
MANE Select: NM_014306
Type: single nucleotide variant
Location: chr22:32412110 (GRCh38)
Gene constraint: LOEUF 0.622 · pLI 0.17 (gnomAD)
Structure: AlphaFold pLDDT 95.66 · 5 PDB
Residue 16: 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-asn16ser (accessed [today's date]).

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