Is CYLC1 p.Pro220Ser (c.658C>T) pathogenic?

CYLC1 p.Pro220Ser (c.658C>T) is classified Uncertain significance in CYLC1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-30). AlphaMissense: likely benign (0.1113); Absent from gnomAD v4.1.

How common is CYLC1 p.Pro220Ser (c.658C>T) in the general population?

CYLC1 p.Pro220Ser (c.658C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CYLC1 p.Pro220Ser (c.658C>T)?

AlphaMissense predicts likely benign (score 0.1113) — an in-silico prediction, not a clinical call.

CYLC1 p.Pro220Ser

c.658C>T · VCV4236665

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1113 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1113	likely benign
REVEL	0.028	moderately benign-leaning
SaProt	LLR -3.16	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 -2.5	GERP -3.2
Regional constraint	o/e 1.40	unconstrained · MANE · 25 kb · p 1.1e-16 · regional, not allelic
Overall
CADD	0.162	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CYLC1
Protein: p.Pro220Ser
Coding: c.658C>T
MANE Select: NM_021118
Type: single nucleotide variant
Location: chrX:83873366 (GRCh38)
Structure: AlphaFold pLDDT 45.68
Residue 220: the 'disordered' region

Full CYLC1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CYLC1 p.Ala554Ser Uncertain significance ★ ⚠ same type
CYLC1 p.Ala595Val Uncertain significance ★ ⚠ same type
CYLC1 p.Ala611Asp Uncertain significance ★ ⚠ same type
CYLC1 p.Arg344Met Uncertain significance ★ ⚠ same type
CYLC1 p.Arg623His Uncertain significance ★ ⚠ same type
CYLC1 p.Arg637Ser Uncertain significance ★ ⚠ same type
CYLC1 p.Asn156Asp Uncertain significance ★ ⚠ same type
CYLC1 p.Asn194Ser 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/cylc1-p-pro220ser (accessed [today's date]).

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