Is CEP20 p.Arg40Cys (c.118C>T) pathogenic?

CEP20 p.Arg40Cys (c.118C>T) is classified Uncertain significance in CEP20 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-04). AlphaMissense: likely benign (0.0754); Very rare (popmax 0.00333%, amr).

How common is CEP20 p.Arg40Cys (c.118C>T) in the general population?

CEP20 p.Arg40Cys (c.118C>T) is very rare (popmax 0.00333%, amr) (gnomAD).

What do computational predictors say about CEP20 p.Arg40Cys (c.118C>T)?

AlphaMissense predicts likely benign (score 0.0754) — an in-silico prediction, not a clinical call.

CEP20 p.Arg40Cys

c.118C>T · rs779775014 · VCV3142757

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0754 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00333%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0754	likely benign
REVEL	0.108	moderately benign-leaning
SaProt	LLR -9.08	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 0.26	GERP -4.5
Regional constraint	o/e 1.07	unconstrained · MANE · 21 kb · p 0.34 · regional, not allelic
Overall
CADD	19.67	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 0.00333% Admixed American · 2/60,010 alleles

Filtering AF 0.000553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000207%

Overall 0.000547% 8/1,461,830 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00333%	30,005
South Asian	0.0022%	45,543
Remaining individualsnot grpmax-eligible	0.0016%	62,510
European (non-Finnish)	0.000254%	393,331

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: CEP20
Protein: p.Arg40Cys
Coding: c.118C>T
MANE Select: NM_144600
dbSNP: rs779775014
Type: single nucleotide variant
Location: chr16:15884116 (GRCh38)
Gene constraint: LOEUF 1.579 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.95
Residue 40: the 'necessary and sufficient for homooligomerization and localization to centrosomes and pericentriolar satellites' region

Full CEP20 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CEP20 p.Ala2Gly Uncertain significance ★ ⚠ same type
CEP20 p.Ala2Val Uncertain significance ★ ⚠ same type
CEP20 p.Ala30Val Uncertain significance ★ ⚠ same type
CEP20 p.Ala35Thr Uncertain significance ★ ⚠ same type
CEP20 p.Ala70Thr Uncertain significance ★ ⚠ same type
CEP20 p.Arg116Cys Uncertain significance ★ ⚠ same type
CEP20 p.Arg141Ser Uncertain significance ★ ⚠ same type
CEP20 p.Arg43Pro 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/cep20-p-arg40cys (accessed [today's date]).

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