Is CABLES1 p.Pro37His (c.110C>A) pathogenic?

CABLES1 p.Pro37His (c.110C>A) is classified Uncertain significance in CABLES1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-26). AlphaMissense: likely benign (0.1288); Absent from gnomAD v4.1.

How common is CABLES1 p.Pro37His (c.110C>A) in the general population?

CABLES1 p.Pro37His (c.110C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CABLES1 p.Pro37His (c.110C>A)?

AlphaMissense predicts likely benign (score 0.1288) — an in-silico prediction, not a clinical call.

CABLES1 p.Pro37His

c.110C>A · VCV4647466

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1288 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,036,218)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1288	likely benign
REVEL	0.074	moderately benign-leaning
SaProt	LLR -11.24	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.81	GERP 0.5, phastCons 0.013
Regional constraint	o/e 1.32	unconstrained · MANE · 355 bp · p 7.9e-05 · regional, not allelic
Overall
CADD	17.99	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

No allele count reported in gnomAD v4.1 (AN 1,036,218). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: CABLES1
Protein: p.Pro37His
Coding: c.110C>A
MANE Select: NM_001100619
Type: single nucleotide variant
Location: chr18:23135872 (GRCh38)
Gene constraint: LOEUF 1.195 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 57.66
Residue 37: 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-pro37his (accessed [today's date]).

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