Is CTBS p.Asp64Glu (c.192T>A) pathogenic?

CTBS p.Asp64Glu (c.192T>A) is classified Uncertain significance in CTBS (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-13). AlphaMissense: ambiguous (0.4084); Ultra-rare (popmax 0.0165%, mid).

How common is CTBS p.Asp64Glu (c.192T>A) in the general population?

CTBS p.Asp64Glu (c.192T>A) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

What do computational predictors say about CTBS p.Asp64Glu (c.192T>A)?

AlphaMissense predicts ambiguous (score 0.4084) — an in-silico prediction, not a clinical call.

CTBS p.Asp64Glu

c.192T>A · rs1647276502 · VCV2334010

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4084 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4084	ambiguous
REVEL	0.116	moderately benign-leaning
SaProt	LLR -8.08	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.1	GERP 1.6, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 19 kb · p 0.43 · regional, not allelic
Overall
CADD	21.8	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 0.0165% Middle Eastern · 1/6,056 alleles

Filtering AF 0.000739% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000276%

Overall 0.000205% 3/1,460,926 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,056
East Asian	0.00446%	22,436

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.Asp64Glu
Coding: c.192T>A
MANE Select: NM_004388
dbSNP: rs1647276502
Type: single nucleotide variant
Location: chr1:84570706 (GRCh38)
Gene constraint: LOEUF 1.084 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.87
Residue 64: 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.Arg277Gln Uncertain significance ★ ⚠ same type
CTBS p.Arg287Cys Uncertain significance ★ ⚠ same type
CTBS p.Arg349Gln 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-asp64glu (accessed [today's date]).

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