Is CTRB1 p.Ser81= (c.243C>T) pathogenic?

CTRB1 p.Ser81= (c.243C>T) is classified Likely benign in CTRB1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-01). Very rare (popmax 0.00698%, sas).

How common is CTRB1 p.Ser81= (c.243C>T) in the general population?

CTRB1 p.Ser81= (c.243C>T) is very rare (popmax 0.00698%, sas) (gnomAD).

CTRB1 p.Ser81=

c.243C>T · VCV3905086

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00698%, sas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.39 · evaluated, not missing
Constraint at this position
Conservation	phyloP -20	GERP -4.3
Overall
CADD	2.606	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00698% South Asian · 5/71,604 alleles

Filtering AF 0.0043% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00379%

Overall 0.0114% 118/1,037,650 alleles · very rare exomes 107/916,570 · genomes 11/121,080 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.12%	834
South Asiangrpmax	0.00698%	14,321
European (non-Finnish)	0.00571%	17,504
African / African-American	0.00515%	19,423
Admixed American	0.00461%	21,678
East Asian	0.00268%	37,262
Remaining individualsnot grpmax-eligible	0.0023%	43,568

Finnish 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.Ser81=
Coding: c.243C>T
MANE Select: NM_001906
Type: single nucleotide variant
Location: chr16:75223147 (GRCh38)
Gene constraint: LOEUF 1.902 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.90
Residue 81: the peptidase s1 domain

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

Similar variants

CTRB1 p.Ser81Phe 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.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

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-ser81 (accessed [today's date]).

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