Is CWC27 p.Ser73Arg (c.219T>G) pathogenic?

CWC27 p.Ser73Arg (c.219T>G) is classified Uncertain significance in CWC27 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-02). AlphaMissense: ambiguous (0.3686); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with CWC27 p.Ser73Arg (c.219T>G)?

CWC27 p.Ser73Arg (c.219T>G) is associated with Inborn genetic diseases (ClinVar).

How common is CWC27 p.Ser73Arg (c.219T>G) in the general population?

CWC27 p.Ser73Arg (c.219T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CWC27 p.Ser73Arg (c.219T>G)?

AlphaMissense predicts ambiguous (score 0.3686) — an in-silico prediction, not a clinical call.

CWC27 p.Ser73Arg

c.219T>G · rs1208853313 · VCV2304730

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3686 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3686	ambiguous
REVEL	0.038	moderately benign-leaning
SaProt	LLR -8.29	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.17	GERP 1.4, phastCons 0.71
Regional constraint	o/e 0.93	unconstrained · MANE · 249 kb · p 0.12 · regional, not allelic
Overall
CADD	19.92	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

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: CWC27
Protein: p.Ser73Arg
Coding: c.219T>G
MANE Select: NM_005869
dbSNP: rs1208853313
Type: single nucleotide variant
Location: chr5:64782000 (GRCh38)
Gene constraint: LOEUF 1.181 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.93 · 9 PDB
Residue 73: the ppiase cyclophilin-type domain; a UniProt-annotated variant site (in rpska); a β-strand

Full CWC27 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CWC27 c.1042+5G>A Uncertain significance ★★ same condition
CWC27 p.Ala102Thr Uncertain significance ★★ ⚠ same condition
CWC27 p.Ala267Thr Uncertain significance ★★ ⚠ same condition
CWC27 p.Arg119Gln Uncertain significance ★★ ⚠ same condition
CWC27 p.Arg282Thr Uncertain significance ★★ ⚠ same condition
CWC27 p.Arg325Gln Uncertain significance ★★ ⚠ same condition
CWC27 p.Arg325Trp Uncertain significance ★★ ⚠ same condition
CWC27 p.Arg361Gly Uncertain significance ★★ ⚠ same condition

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/cwc27-p-ser73arg (accessed [today's date]).

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