Is CABLES1 p.Pro39Arg (c.116C>G) pathogenic?

CABLES1 p.Pro39Arg (c.116C>G) is classified Uncertain significance in CABLES1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-09). AlphaMissense: likely benign (0.1016); Rare (popmax 0.171%, afr).

How common is CABLES1 p.Pro39Arg (c.116C>G) in the general population?

CABLES1 p.Pro39Arg (c.116C>G) is rare (popmax 0.171%, afr) (gnomAD).

What do computational predictors say about CABLES1 p.Pro39Arg (c.116C>G)?

AlphaMissense predicts likely benign (score 0.1016) — an in-silico prediction, not a clinical call.

CABLES1 p.Pro39Arg

c.116C>G · rs1046665983 · VCV3136220

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1016 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.171%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1016	likely benign
REVEL	0.061	moderately benign-leaning
SaProt	LLR -9.30	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 -0.84	GERP -0.41, phastCons 0.002
Regional constraint	o/e 1.32	unconstrained · MANE · 355 bp · p 7.9e-05 · regional, not allelic
Overall
CADD	20.4	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 0.171% African / African-American · 99/57,880 alleles

Filtering AF 0.144% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.134%

Overall 0.0101% 106/1,044,346 alleles · rare exomes 33/897,554 · genomes 73/146,792 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.171%	585
Middle Eastern	0.0897%	1,115
Admixed American	0.0109%	9,133
Remaining individualsnot grpmax-eligible	0.0061%	16,400
European (non-Finnish)	0.000115%	871,931

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: CABLES1
Protein: p.Pro39Arg
Coding: c.116C>G
MANE Select: NM_001100619
dbSNP: rs1046665983
Type: single nucleotide variant
Location: chr18:23135878 (GRCh38)
Gene constraint: LOEUF 1.195 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 57.66
Residue 39: the 'interaction with tdrd7' region; the 'disordered' region

Full CABLES1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CABLES1 p.Asp75= Likely benign ★★ same type
CABLES1 p.Ala104Val Uncertain significance ★ ⚠ same type
CABLES1 p.Ala114Val Uncertain significance ★ ⚠ same type
CABLES1 p.Ala12Pro Uncertain significance ★ ⚠ same type
CABLES1 p.Ala12Ser Uncertain significance ★ ⚠ same type
CABLES1 p.Ala155Ser Uncertain significance ★ ⚠ same type
CABLES1 p.Ala155Val Uncertain significance ★ ⚠ same type
CABLES1 p.Ala172Thr 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/cables1-p-pro39arg (accessed [today's date]).

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