Is CABLES1 p.Ser200Pro (c.598T>C) pathogenic?

CABLES1 p.Ser200Pro (c.598T>C) is classified Likely benign in CABLES1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-31). AlphaMissense: likely benign (0.0488); Very rare (popmax 0.00143%, afr).

How common is CABLES1 p.Ser200Pro (c.598T>C) in the general population?

CABLES1 p.Ser200Pro (c.598T>C) is very rare (popmax 0.00143%, afr) (gnomAD).

What do computational predictors say about CABLES1 p.Ser200Pro (c.598T>C)?

AlphaMissense predicts likely benign (score 0.0488) — an in-silico prediction, not a clinical call.

CABLES1 p.Ser200Pro

c.598T>C · VCV4217634

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0488 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00143%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0488	likely benign
REVEL	0.023	moderately benign-leaning
SaProt	LLR -5.95	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 -0.25	GERP -2
Regional constraint	o/e 0.85	unconstrained · MANE · 118 kb · p 0.00017 · regional, not allelic
Overall
CADD	3.305	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 0.00143% African / African-American · 1/69,982 alleles

Overall 7.35e-05% 1/1,361,464 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: CABLES1
Protein: p.Ser200Pro
Coding: c.598T>C
MANE Select: NM_001100619
Type: single nucleotide variant
Location: chr18:23136360 (GRCh38)
Gene constraint: LOEUF 1.195 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 57.66
Residue 200: the 'interaction with cdk3' 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-ser200pro (accessed [today's date]).

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