Is CABLES1 p.Pro55Arg (c.164C>G) pathogenic?

CABLES1 p.Pro55Arg (c.164C>G) is classified Uncertain significance in CABLES1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-16). AlphaMissense: likely benign (0.1214); Very rare (popmax 0.00588%, eas).

How common is CABLES1 p.Pro55Arg (c.164C>G) in the general population?

CABLES1 p.Pro55Arg (c.164C>G) is very rare (popmax 0.00588%, eas) (gnomAD).

What do computational predictors say about CABLES1 p.Pro55Arg (c.164C>G)?

AlphaMissense predicts likely benign (score 0.1214) — an in-silico prediction, not a clinical call.

CABLES1 p.Pro55Arg

c.164C>G · rs1598791278 · VCV3136224

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1214 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00588%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1214	likely benign
REVEL	0.067	moderately benign-leaning
SaProt	LLR -6.44	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 4.1	GERP 0.62, phastCons 1
Regional constraint	o/e 1.32	unconstrained · MANE · 355 bp · p 7.9e-05 · regional, not allelic
Overall
CADD	22.2	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 0.00588% East Asian · 1/17,018 alleles

Overall 9.05e-05% 1/1,105,072 alleles · very rare exomes 0/957,418 · genomes 1/147,654 · joint denominator

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.Pro55Arg
Coding: c.164C>G
MANE Select: NM_001100619
dbSNP: rs1598791278
Type: single nucleotide variant
Location: chr18:23135926 (GRCh38)
Gene constraint: LOEUF 1.195 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 57.66
Residue 55: 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-pro55arg (accessed [today's date]).

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