Is CABLES2 p.Ala4Val (c.11C>T) pathogenic?

CABLES2 p.Ala4Val (c.11C>T) is classified Uncertain significance in CABLES2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-08). AlphaMissense: likely pathogenic (0.6329); Very rare (popmax 0.00658%, amr).

How common is CABLES2 p.Ala4Val (c.11C>T) in the general population?

CABLES2 p.Ala4Val (c.11C>T) is very rare (popmax 0.00658%, amr) (gnomAD).

What do computational predictors say about CABLES2 p.Ala4Val (c.11C>T)?

AlphaMissense predicts likely pathogenic (score 0.6329) — an in-silico prediction, not a clinical call.

CABLES2 p.Ala4Val

c.11C>T · rs1222512037 · VCV3136237

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6329 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00658%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6329	likely pathogenic
REVEL	0.111	moderately benign-leaning
SaProt	LLR -9.25	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.4	GERP 0.75, phastCons 1
Regional constraint	o/e 1.64	unconstrained · MANE · 225 bp · p 1.3e-08 · regional, not allelic
Overall
CADD	22.7	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 0.00658% Admixed American · 1/15,194 alleles

Filtering AF 0.000175% ClinGen BA1/BS1 input FAF95, joint · FAF99 4.9e-05%

Overall 0.000698% 4/572,846 alleles · very rare exomes 3/426,880 · genomes 1/145,966 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00658%	15,194
European (non-Finnish)	0.000657%	152,180

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.Ala4Val
Coding: c.11C>T
MANE Select: NM_031215
dbSNP: rs1222512037
Type: single nucleotide variant
Location: chr20:62407266 (GRCh38)
Gene constraint: LOEUF 1 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 61.39
Residue 4: the 'disordered' region

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

Similar variants

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
CABLES2 p.Ala287Val Uncertain significance ★ ⚠ same type
CABLES2 p.Ala35Val 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-ala4val (accessed [today's date]).

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