Is CEP20 p.Ala30Val (c.89C>T) pathogenic?

CEP20 p.Ala30Val (c.89C>T) is classified Uncertain significance in CEP20 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-10). AlphaMissense: likely pathogenic (0.6364); Very rare (popmax 0.000254%, nfe).

How common is CEP20 p.Ala30Val (c.89C>T) in the general population?

CEP20 p.Ala30Val (c.89C>T) is very rare (popmax 0.000254%, nfe) (gnomAD).

What do computational predictors say about CEP20 p.Ala30Val (c.89C>T)?

AlphaMissense predicts likely pathogenic (score 0.6364) — an in-silico prediction, not a clinical call.

CEP20 p.Ala30Val

c.89C>T · VCV4000824

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6364 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000254%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.6364	likely pathogenic
REVEL	0.502	indeterminate
SaProt	LLR -11.76	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.3, phastCons 1
Regional constraint	o/e 1.07	unconstrained · MANE · 21 kb · p 0.34 · regional, not allelic
Overall
CADD	29.5	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.000254% European (non-Finnish) · 3/1,179,976 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.00335% 54/1,613,966 alleles · very rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.0765%	1,307
Remaining individualsnot grpmax-eligible	0.0032%	31,239
European (non-Finnish)grpmax	0.000254%	393,326

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ala30Val
Coding: c.89C>T
MANE Select: NM_144600
Type: single nucleotide variant
Location: chr16:15884145 (GRCh38)
Gene constraint: LOEUF 1.579 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.95
Residue 30: 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.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-ala30val (accessed [today's date]).

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