Is CABLES1 p.Pro147Ser (c.439C>T) pathogenic?

CABLES1 p.Pro147Ser (c.439C>T) is classified Uncertain significance in CABLES1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-13). AlphaMissense: likely benign (0.0649); Ultra-rare (popmax 0.0705%, afr).

How common is CABLES1 p.Pro147Ser (c.439C>T) in the general population?

CABLES1 p.Pro147Ser (c.439C>T) is ultra-rare (popmax 0.0705%, afr) (gnomAD).

What do computational predictors say about CABLES1 p.Pro147Ser (c.439C>T)?

AlphaMissense predicts likely benign (score 0.0649) — an in-silico prediction, not a clinical call.

CABLES1 p.Pro147Ser

c.439C>T · rs1010505803 · VCV3136229

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0649 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0705%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0649	likely benign
REVEL	0.042	moderately benign-leaning
SaProt	LLR -6.59	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 2.9	GERP -0.32, phastCons 0.99
Regional constraint	o/e 0.85	unconstrained · MANE · 118 kb · p 0.00017 · regional, not allelic
Overall
CADD	15.24	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 0.0705% African / African-American · 45/63,830 alleles

Filtering AF 0.0541% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0483%

Overall 0.00408% 51/1,251,300 alleles · ultra-rare exomes 21/1,099,710 · genomes 30/151,590 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0705%	1,418
Admixed American	0.00431%	23,228
European (non-Finnish)	0.0005%	200,189

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.Pro147Ser
Coding: c.439C>T
MANE Select: NM_001100619
dbSNP: rs1010505803
Type: single nucleotide variant
Location: chr18:23136201 (GRCh38)
Gene constraint: LOEUF 1.195 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 57.66

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

Similar variants

CABLES1 p.Pro147Leu Uncertain significance ★ ⚠ same residue
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

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-pro147ser (accessed [today's date]).

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