Is CTBS p.Arg277Gln (c.830G>A) pathogenic?

CTBS p.Arg277Gln (c.830G>A) is classified Uncertain significance in CTBS (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-07). AlphaMissense: likely benign (0.1298); Ultra-rare (popmax 0.066%, afr).

How common is CTBS p.Arg277Gln (c.830G>A) in the general population?

CTBS p.Arg277Gln (c.830G>A) is ultra-rare (popmax 0.066%, afr) (gnomAD).

What do computational predictors say about CTBS p.Arg277Gln (c.830G>A)?

AlphaMissense predicts likely benign (score 0.1298) — an in-silico prediction, not a clinical call.

CTBS p.Arg277Gln

c.830G>A · VCV3498097

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1298 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.066%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1298	likely benign
REVEL	0.143	moderately benign-leaning
SaProt	LLR -7.16	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.3	GERP -0.18, phastCons 0.9
Regional constraint	o/e 0.96	unconstrained · MANE · 19 kb · p 0.43 · regional, not allelic
Overall
CADD	20.6	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 0.066% African / African-American · 48/72,678 alleles

Filtering AF 0.0512% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0458%

Overall 0.00749% 118/1,574,832 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.066%	1,514
Admixed American	0.00945%	10,583
Remaining individualsnot grpmax-eligible	0.00826%	12,110
European (non-Finnish)	0.00516%	19,380

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: CTBS
Protein: p.Arg277Gln
Coding: c.830G>A
MANE Select: NM_004388
Type: single nucleotide variant
Location: chr1:84563384 (GRCh38)
Gene constraint: LOEUF 1.084 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.87
Residue 277: the gh18 domain

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

Similar variants

CTBS p.Asn357= Benign ★★ same type
CTBS p.Ala284Thr Uncertain significance ★ ⚠ same type
CTBS p.Ala32Val Uncertain significance ★ ⚠ same type
CTBS p.Arg169Ser Uncertain significance ★ ⚠ same type
CTBS p.Arg189Gly Uncertain significance ★ ⚠ same type
CTBS p.Arg287Cys Uncertain significance ★ ⚠ same type
CTBS p.Arg349Gln Uncertain significance ★ ⚠ same type
CTBS p.Arg3Gln 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/ctbs-p-arg277gln (accessed [today's date]).

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