Is CABLES2 p.Ala9Val (c.26C>T) pathogenic?

CABLES2 p.Ala9Val (c.26C>T) is classified Uncertain significance in CABLES2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-24). AlphaMissense: likely benign (0.228); Very rare (popmax 0.000531%, nfe).

How common is CABLES2 p.Ala9Val (c.26C>T) in the general population?

CABLES2 p.Ala9Val (c.26C>T) is very rare (popmax 0.000531%, nfe) (gnomAD).

What do computational predictors say about CABLES2 p.Ala9Val (c.26C>T)?

AlphaMissense predicts likely benign (score 0.228) — an in-silico prediction, not a clinical call.

CABLES2 p.Ala9Val

c.26C>T · rs1988318428 · VCV3136240

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.228 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000531%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.228	likely benign
REVEL	0.061	moderately benign-leaning
SaProt	LLR -8.77	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 4	GERP -0.59, phastCons 0.93
Regional constraint	o/e 1.64	unconstrained · MANE · 225 bp · p 1.3e-08 · regional, not allelic
Overall
CADD	12.08	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 0.000531% European (non-Finnish) · 3/565,334 alleles

Filtering AF 0.000141% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.9e-05%

Overall 0.00055% 3/545,710 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: CABLES2
Protein: p.Ala9Val
Coding: c.26C>T
MANE Select: NM_031215
dbSNP: rs1988318428
Type: single nucleotide variant
Location: chr20:62407251 (GRCh38)
Gene constraint: LOEUF 1 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 61.39
Residue 9: the 'disordered' region

Full CABLES2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CABLES2 p.Ala9Ser Uncertain significance ★ ⚠ same residue
CABLES2 p.Ala9Thr Uncertain significance ★ ⚠ same residue
CABLES2 p.Arg128His Uncertain significance ★★ ⚠ same type
CABLES2 p.Leu103= Benign ★★ same type
CABLES2 p.Ala13Asp Uncertain significance ★ ⚠ same type
CABLES2 p.Ala17Thr Uncertain significance ★ ⚠ same type
CABLES2 p.Ala23Asp Uncertain significance ★ ⚠ same type
CABLES2 p.Ala23Thr 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/cables2-p-ala9val (accessed [today's date]).

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