Is CTBS p.Asp179Val (c.536A>T) pathogenic?

CTBS p.Asp179Val (c.536A>T) is classified Uncertain significance in CTBS (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-19). AlphaMissense: likely pathogenic (0.8592); Very rare (popmax 0.000611%, nfe).

How common is CTBS p.Asp179Val (c.536A>T) in the general population?

CTBS p.Asp179Val (c.536A>T) is very rare (popmax 0.000611%, nfe) (gnomAD).

What do computational predictors say about CTBS p.Asp179Val (c.536A>T)?

AlphaMissense predicts likely pathogenic (score 0.8592) — an in-silico prediction, not a clinical call.

CTBS p.Asp179Val

c.536A>T · VCV3837078

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8592 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000611%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.8592	likely pathogenic · top 10% in CTBS
REVEL	0.352	indeterminate
SaProt	LLR -9.81	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.2	GERP 0.67, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 19 kb · p 0.43 · regional, not allelic
Overall
CADD	26.2	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 0.000611% European (non-Finnish) · 7/1,145,302 alleles

Filtering AF 0.000254% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000163%

Overall 0.000454% 7/1,542,642 alleles · very rare

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.Asp179Val
Coding: c.536A>T
MANE Select: NM_004388
Type: single nucleotide variant
Location: chr1:84566002 (GRCh38)
Gene constraint: LOEUF 1.084 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.87
Residue 179: 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-asp179val (accessed [today's date]).

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