Is CEP20 p.Leu7Phe (c.21G>T) pathogenic?

CEP20 p.Leu7Phe (c.21G>T) is classified Uncertain significance in CEP20 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-31). AlphaMissense: likely pathogenic (0.6944); Ultra-rare (popmax 0.0312%, eas).

How common is CEP20 p.Leu7Phe (c.21G>T) in the general population?

CEP20 p.Leu7Phe (c.21G>T) is ultra-rare (popmax 0.0312%, eas) (gnomAD).

What do computational predictors say about CEP20 p.Leu7Phe (c.21G>T)?

AlphaMissense predicts likely pathogenic (score 0.6944) — an in-silico prediction, not a clinical call.

CEP20 p.Leu7Phe

c.21G>T · rs780495622 · VCV3142762

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6944 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0312%, eas)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.6944	likely pathogenic
REVEL	0.301	indeterminate
SaProt	LLR -12.23	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 -0.007	GERP -3, phastCons 0.78
Regional constraint	o/e 1.07	unconstrained · MANE · 21 kb · p 0.34 · regional, not allelic
Overall
CADD	22.2	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 0.0312% East Asian · 14/44,876 alleles

Filtering AF 0.0188% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0151%

Overall 0.000929% 15/1,614,082 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0312%	3,205
Admixed American	0.00167%	60,010

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.Leu7Phe
Coding: c.21G>T
MANE Select: NM_144600
dbSNP: rs780495622
Type: single nucleotide variant
Location: chr16:15888565 (GRCh38)
Gene constraint: LOEUF 1.579 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.95
Residue 7: 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.Arg40Cys 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-leu7phe (accessed [today's date]).

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