Is CEP72 p.Val9Met (c.25G>A) pathogenic?

CEP72 p.Val9Met (c.25G>A) is classified Uncertain significance in CEP72 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-15). AlphaMissense: likely pathogenic (0.6507); Very rare (popmax 0.00376%, sas).

How common is CEP72 p.Val9Met (c.25G>A) in the general population?

CEP72 p.Val9Met (c.25G>A) is very rare (popmax 0.00376%, sas) (gnomAD).

What do computational predictors say about CEP72 p.Val9Met (c.25G>A)?

AlphaMissense predicts likely pathogenic (score 0.6507) — an in-silico prediction, not a clinical call.

CEP72 p.Val9Met

c.25G>A · VCV3266259

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6507 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00376%, sas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6507	likely pathogenic · top 10% in CEP72
REVEL	0.021	moderately benign-leaning
SaProt	LLR -6.87	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.65	GERP -1.5, phastCons 0.79
Regional constraint	o/e 1.10	unconstrained · MANE · 41 kb · p 0.005 · regional, not allelic
Overall
CADD	14.07	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 0.00376% South Asian · 3/79,690 alleles

Filtering AF 0.001% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000477%

Overall 0.000299% 4/1,339,462 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00376%	26,563
European (non-Finnish)	8.88e-05%	1,125,783

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.Val9Met
Coding: c.25G>A
MANE Select: NM_018140
Type: single nucleotide variant
Location: chr5:612386 (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.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
CEP72 p.Ala386Val 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-val9met (accessed [today's date]).

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