Is CEP72 p.Pro6Ala (c.16C>G) pathogenic?

CEP72 p.Pro6Ala (c.16C>G) is classified Uncertain significance in CEP72 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-22). AlphaMissense: likely benign (0.0755); Very rare (popmax 0.00195%, nfe).

How common is CEP72 p.Pro6Ala (c.16C>G) in the general population?

CEP72 p.Pro6Ala (c.16C>G) is very rare (popmax 0.00195%, nfe) (gnomAD).

What do computational predictors say about CEP72 p.Pro6Ala (c.16C>G)?

AlphaMissense predicts likely benign (score 0.0755) — an in-silico prediction, not a clinical call.

CEP72 p.Pro6Ala

c.16C>G · VCV4226482

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0755 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00195%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0755	likely benign
REVEL	0.108	moderately benign-leaning
SaProt	LLR -6.01	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 -0.5	GERP -1.6
Regional constraint	o/e 1.10	unconstrained · MANE · 41 kb · p 0.005 · regional, not allelic
Overall
CADD	0.595	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 0.00195% European (non-Finnish) · 22/1,125,738 alleles

Filtering AF 0.00128% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00109%

Overall 0.00164% 22/1,339,092 alleles · very rare

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: CEP72
Protein: p.Pro6Ala
Coding: c.16C>G
MANE Select: NM_018140
Type: single nucleotide variant
Location: chr5:612377 (GRCh38)
Gene constraint: LOEUF 1.409 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 65.74

Full CEP72 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CEP72 p.Pro6Ser Uncertain significance ★ ⚠ same residue
CEP72 p.Ala192Val Uncertain significance ★★ ⚠ same type
CEP72 p.Asp135= Benign ★★ same type
TPPP p.Ala148= Likely benign ★★ same type
TPPP p.His207= Benign ★★ same type
TPPP p.Thr167= Benign ★★ same type
CEP72 p.Ala17Gly Uncertain significance ★ ⚠ same type
CEP72 p.Ala2Gly 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/cep72-p-pro6ala (accessed [today's date]).

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