Is CTRB1 p.Ala150Thr (c.448G>A) pathogenic?

CTRB1 p.Ala150Thr (c.448G>A) is classified Likely benign in CTRB1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-28). AlphaMissense: likely benign (0.0966); Ultra-rare (popmax 0.0405%, mid).

How common is CTRB1 p.Ala150Thr (c.448G>A) in the general population?

CTRB1 p.Ala150Thr (c.448G>A) is ultra-rare (popmax 0.0405%, mid) (gnomAD).

What do computational predictors say about CTRB1 p.Ala150Thr (c.448G>A)?

AlphaMissense predicts likely benign (score 0.0966) — an in-silico prediction, not a clinical call.

CTRB1 p.Ala150Thr

c.448G>A · rs1328058568 · VCV3078723

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0966 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0405%, mid)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.0966	likely benign
REVEL	0.304	indeterminate
SaProt	LLR -9.89	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 -1.3	GERP -2
Regional constraint	o/e 0.13	constrained · MANE · 1,089 bp · p 5.9e-17 · regional, not allelic
Overall
CADD	9.521	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 0.0405% Middle Eastern · 1/2,470 alleles

Filtering AF 0.0145% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0108%

Overall 0.00685% 41/598,104 alleles · ultra-rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0515%	1,941
Middle Easterngrpmax	0.0405%	2,470
East Asian	0.0279%	3,580
Admixed American	0.00382%	26,204
European (non-Finnish)	0.00381%	26,236
South Asian	0.00192%	52,130

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ala150Thr
Coding: c.448G>A
MANE Select: NM_001906
dbSNP: rs1328058568
Type: single nucleotide variant
Location: chr16:75223580 (GRCh38)
Gene constraint: LOEUF 1.902 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.90
Residue 150: the peptidase s1 domain

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

Similar variants

CTRB1 p.Ala150Ser Uncertain significance ★ ⚠ same residue
CTRB1 p.Ala104Asp Uncertain significance ★ ⚠ same type
CTRB1 p.Ala138Thr Uncertain significance ★ ⚠ same type
CTRB1 p.Ala144Thr 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-ala150thr (accessed [today's date]).

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