Is CYLC1 p.Pro162Ser (c.484C>T) pathogenic?

CYLC1 p.Pro162Ser (c.484C>T) is classified Uncertain significance in CYLC1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-07-14). AlphaMissense: likely benign (0.0925); Very rare (popmax 0.000112%, nfe).

How common is CYLC1 p.Pro162Ser (c.484C>T) in the general population?

CYLC1 p.Pro162Ser (c.484C>T) is very rare (popmax 0.000112%, nfe) (gnomAD).

What do computational predictors say about CYLC1 p.Pro162Ser (c.484C>T)?

AlphaMissense predicts likely benign (score 0.0925) — an in-silico prediction, not a clinical call.

CYLC1 p.Pro162Ser

c.484C>T · rs748109334 · VCV2237011

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0925 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000112%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0925	likely benign
REVEL	0.037	moderately benign-leaning
SaProt	LLR -5.60	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 -1.7	GERP -0.96
Regional constraint	o/e 1.40	unconstrained · MANE · 25 kb · p 1.1e-16 · regional, not allelic
Overall
CADD	1.422	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 0.000112% European (non-Finnish) · 1/892,067 alleles

Overall 9.15e-05% 1/1,092,480 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: CYLC1
Protein: p.Pro162Ser
Coding: c.484C>T
MANE Select: NM_021118
dbSNP: rs748109334
Type: single nucleotide variant
Location: chrX:83873192 (GRCh38)
Structure: AlphaFold pLDDT 45.68
Residue 162: 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-pro162ser (accessed [today's date]).

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