Is CYLC2 p.Pro19Thr (c.55C>A) pathogenic?

CYLC2 p.Pro19Thr (c.55C>A) is classified Uncertain significance in CYLC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-27). AlphaMissense: likely pathogenic (0.7152); Absent from gnomAD v4.1.

How common is CYLC2 p.Pro19Thr (c.55C>A) in the general population?

CYLC2 p.Pro19Thr (c.55C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CYLC2 p.Pro19Thr (c.55C>A)?

AlphaMissense predicts likely pathogenic (score 0.7152) — an in-silico prediction, not a clinical call.

CYLC2 p.Pro19Thr

c.55C>A · VCV3837735

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7152 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,556,936)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.7152	likely pathogenic · top 10% in CYLC2
REVEL	0.178	moderately benign-leaning
SaProt	LLR -6.94	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.8	GERP 1.8, phastCons 1
Regional constraint	o/e 1.26	unconstrained · MANE · 10 kb · p 1.8e-07 · regional, not allelic
Overall
CADD	25.7	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 1,556,936). 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: CYLC2
Protein: p.Pro19Thr
Coding: c.55C>A
MANE Select: NM_001340
Type: single nucleotide variant
Location: chr9:103001615 (GRCh38)
Gene constraint: LOEUF 1.608 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 50.39

Full CYLC2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CYLC2 p.Asp330His Uncertain significance ★★ ⚠ same type
CYLC2 p.Ala175Val Uncertain significance ★ ⚠ same type
CYLC2 p.Ala296Thr Uncertain significance ★ ⚠ same type
CYLC2 p.Ala327Glu Uncertain significance ★ ⚠ same type
CYLC2 p.Arg42Gln Uncertain significance ★ ⚠ same type
CYLC2 p.Arg55Gln Uncertain significance ★ ⚠ same type
CYLC2 p.Arg55Trp Uncertain significance ★ ⚠ same type
CYLC2 p.Arg71Gly 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/cylc2-p-pro19thr (accessed [today's date]).

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