Is CABLES2 p.Pro10Thr (c.28C>A) pathogenic?

CABLES2 p.Pro10Thr (c.28C>A) is classified Uncertain significance in CABLES2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-11). AlphaMissense: likely benign (0.1104); Ultra-rare (popmax 0.0925%, afr).

How common is CABLES2 p.Pro10Thr (c.28C>A) in the general population?

CABLES2 p.Pro10Thr (c.28C>A) is ultra-rare (popmax 0.0925%, afr) (gnomAD).

What do computational predictors say about CABLES2 p.Pro10Thr (c.28C>A)?

AlphaMissense predicts likely benign (score 0.1104) — an in-silico prediction, not a clinical call.

CABLES2 p.Pro10Thr

c.28C>A · rs1468540907 · VCV2369506

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1104 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0925%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1104	likely benign
REVEL	0.033	moderately benign-leaning
SaProt	LLR -9.48	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 -0.23	GERP -1.5
Regional constraint	o/e 1.64	unconstrained · MANE · 225 bp · p 1.3e-08 · regional, not allelic
Overall
CADD	4.381	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 0.0925% African / African-American · 47/50,830 alleles

Filtering AF 0.0714% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.064%

Overall 0.00857% 60/699,808 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0925%	1,081
Middle Eastern	0.0699%	1,430
South Asian	0.0381%	2,625
Remaining individualsnot grpmax-eligible	0.0099%	10,102
European (non-Finnish)	0.000698%	143,203

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.Pro10Thr
Coding: c.28C>A
MANE Select: NM_031215
dbSNP: rs1468540907
Type: single nucleotide variant
Location: chr20:62407249 (GRCh38)
Gene constraint: LOEUF 1 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 61.39
Residue 10: the 'disordered' region

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

Similar variants

CABLES2 p.Pro10Ala Uncertain significance ★ ⚠ same residue
CABLES2 p.Pro10Arg Uncertain significance ★ ⚠ same residue
CABLES2 p.Pro10Gln Uncertain significance ★ ⚠ same residue
CABLES2 p.Pro10Leu 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

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-pro10thr (accessed [today's date]).

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