Is CTRB1 p.Asp196Asn (c.586G>A) pathogenic?

CTRB1 p.Asp196Asn (c.586G>A) is classified Uncertain significance in CTRB1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-26). AlphaMissense: likely benign (0.1628); Very rare (popmax 0.00291%, afr).

How common is CTRB1 p.Asp196Asn (c.586G>A) in the general population?

CTRB1 p.Asp196Asn (c.586G>A) is very rare (popmax 0.00291%, afr) (gnomAD).

What do computational predictors say about CTRB1 p.Asp196Asn (c.586G>A)?

AlphaMissense predicts likely benign (score 0.1628) — an in-silico prediction, not a clinical call.

CTRB1 p.Asp196Asn

c.586G>A · rs1379132184 · VCV2207582

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1628 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00291%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1628	likely benign
REVEL	0.292	indeterminate
SaProt	LLR -9.26	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -6.3	GERP -4.1
Regional constraint	o/e 0.70	unconstrained · MANE · 115 bp · p 0.029 · regional, not allelic
Overall
CADD	8.21	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 0.00291% African / African-American · 2/68,652 alleles

Filtering AF 0.00171% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00147%

Overall 0.00225% 33/1,466,332 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00291%	34,326
European (non-Finnish)	0.0025%	40,044
South Asian	0.00247%	40,535
Admixed American	0.00206%	48,548
Finnishnot grpmax-eligible	0.00173%	57,674

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.Asp196Asn
Coding: c.586G>A
MANE Select: NM_001906
dbSNP: rs1379132184
Type: single nucleotide variant
Location: chr16:75224144 (GRCh38)
Gene constraint: LOEUF 1.902 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.90
Residue 196: a disulfide bond; 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-asp196asn (accessed [today's date]).

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