Is CTRB2 p.Ser207Phe (c.620C>T) pathogenic?

CTRB2 p.Ser207Phe (c.620C>T) is classified Uncertain significance in CTRB2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-24). AlphaMissense: likely pathogenic (0.9285); Very rare (popmax 0.00263%, amr).

How common is CTRB2 p.Ser207Phe (c.620C>T) in the general population?

CTRB2 p.Ser207Phe (c.620C>T) is very rare (popmax 0.00263%, amr) (gnomAD).

What do computational predictors say about CTRB2 p.Ser207Phe (c.620C>T)?

AlphaMissense predicts likely pathogenic (score 0.9285) — an in-silico prediction, not a clinical call.

CTRB2 p.Ser207Phe

c.620C>T · VCV4235787

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9285 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00263%, amr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9285	likely pathogenic
REVEL	0.827	moderately pathogenic-leaning
SaProt	LLR -14.57	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2, phastCons 1
Regional constraint	o/e 1.32	unconstrained · MANE · 639 bp · p 0.0022 · regional, not allelic
Overall
CADD	26.1	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.00263% Admixed American · 1/37,982 alleles

Filtering AF 0.000777% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000608%

Overall 0.00121% 17/1,400,388 alleles · very rare exomes 17/1,261,738 · genomes 0/138,650 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.00371%	26,925
Admixed Americangrpmax	0.00263%	37,982
European (non-Finnish)	0.00134%	74,708

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: CTRB2
Protein: p.Ser207Phe
Coding: c.620C>T
MANE Select: NM_001025200
Type: single nucleotide variant
Location: chr16:75204783 (GRCh38)
Gene constraint: LOEUF 1.168 · pLI 0.36 (gnomAD)
Structure: AlphaFold pLDDT 91.79
Residue 207: the peptidase s1 domain

Full CTRB2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

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CTRB2 p.Ala138Thr Uncertain significance ★ ⚠ same type
CTRB2 p.Ala244Thr Uncertain significance ★ ⚠ same type
CTRB2 p.Arg131His Uncertain significance ★ ⚠ same type
CTRB2 p.Arg236Cys Uncertain significance ★ ⚠ same type
CTRB2 p.Arg236His Uncertain significance ★ ⚠ same type
CTRB2 p.Arg248Cys Uncertain significance ★ ⚠ same type
CTRB2 p.Asn167Tyr 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/ctrb2-p-ser207phe (accessed [today's date]).

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