Is CEP20 p.Ala2Val (c.5C>T) pathogenic?

CEP20 p.Ala2Val (c.5C>T) is classified Uncertain significance in CEP20 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-30). AlphaMissense: likely pathogenic (0.8213); Very rare (popmax 0.00695%, nfe).

How common is CEP20 p.Ala2Val (c.5C>T) in the general population?

CEP20 p.Ala2Val (c.5C>T) is very rare (popmax 0.00695%, nfe) (gnomAD).

What do computational predictors say about CEP20 p.Ala2Val (c.5C>T)?

AlphaMissense predicts likely pathogenic (score 0.8213) — an in-silico prediction, not a clinical call.

CEP20 p.Ala2Val

c.5C>T · rs775219497 · VCV3142771

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8213 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00695%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8213	likely pathogenic
REVEL	0.132	moderately benign-leaning
SaProt	LLR -10.28	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.5	GERP 2.2, phastCons 1
Regional constraint	o/e 1.07	unconstrained · MANE · 21 kb · p 0.34 · regional, not allelic
Overall
CADD	32.0	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

Grpmax group 0.00695% European (non-Finnish) · 82/1,180,014 alleles

Filtering AF 0.00571% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00525%

Overall 0.00545% 88/1,613,978 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00695%	14,390
Admixed American	0.005%	19,999
Remaining individualsnot grpmax-eligible	0.0016%	62,484
African / African-American	0.00133%	74,914
South Asian	0.0011%	91,082

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.Ala2Val
Coding: c.5C>T
MANE Select: NM_144600
dbSNP: rs775219497
Type: single nucleotide variant
Location: chr16:15888581 (GRCh38)
Gene constraint: LOEUF 1.579 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.95
Residue 2: 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 residue
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.Arg40Cys 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-ala2val (accessed [today's date]).

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