Is CTRB1 p.Arg193Lys (c.578G>A) pathogenic?

CTRB1 p.Arg193Lys (c.578G>A) is classified Likely benign in CTRB1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-01-07). AlphaMissense: likely benign (0.1141); Ultra-rare (popmax 0.0872%, afr).

How common is CTRB1 p.Arg193Lys (c.578G>A) in the general population?

CTRB1 p.Arg193Lys (c.578G>A) is ultra-rare (popmax 0.0872%, afr) (gnomAD).

What do computational predictors say about CTRB1 p.Arg193Lys (c.578G>A)?

AlphaMissense predicts likely benign (score 0.1141) — an in-silico prediction, not a clinical call.

CTRB1 p.Arg193Lys

c.578G>A · rs1468304725 · VCV2402901

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1141 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0872%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1141	likely benign
REVEL	0.175	moderately benign-leaning
SaProt	LLR -7.42	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -7.6	GERP -4.1
Regional constraint	o/e 0.70	unconstrained · MANE · 115 bp · p 0.029 · regional, not allelic
Overall
CADD	0.027	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 0.0872% African / African-American · 59/67,660 alleles

Filtering AF 0.0693% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.063%

Overall 0.00497% 72/1,449,236 alleles · ultra-rare exomes 44/1,306,770 · genomes 28/142,466 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0872%	1,147
Remaining individualsnot grpmax-eligible	0.0196%	5,105
Admixed American	0.00207%	48,374
European (non-Finnish)	9.37e-05%	1,066,788

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: CTRB1
Protein: p.Arg193Lys
Coding: c.578G>A
MANE Select: NM_001906
dbSNP: rs1468304725
Type: single nucleotide variant
Location: chr16:75224136 (GRCh38)
Gene constraint: LOEUF 1.902 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.90
Residue 193: the peptidase s1 domain

Full CTRB1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CTRB1 p.Ala104Asp Uncertain significance ★ ⚠ same type
CTRB1 p.Ala138Thr Uncertain significance ★ ⚠ same type
CTRB1 p.Ala144Thr Uncertain significance ★ ⚠ same type
CTRB1 p.Ala150Ser Uncertain significance ★ ⚠ same type
CTRB1 p.Ala177Val Uncertain significance ★ ⚠ same type
CTRB1 p.Ala261Val Uncertain significance ★ ⚠ same type
CTRB1 p.Ala40Thr Uncertain significance ★ ⚠ same type
CTRB1 p.Arg131Cys 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/ctrb1-p-arg193lys (accessed [today's date]).

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