Is CEP72 p.Pro112Leu (c.335C>T) pathogenic?

CEP72 p.Pro112Leu (c.335C>T) is classified Uncertain significance in CEP72 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-25). AlphaMissense: likely pathogenic (0.7332); Absent from gnomAD v4.1.

How common is CEP72 p.Pro112Leu (c.335C>T) in the general population?

CEP72 p.Pro112Leu (c.335C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CEP72 p.Pro112Leu (c.335C>T)?

AlphaMissense predicts likely pathogenic (score 0.7332) — an in-silico prediction, not a clinical call.

CEP72 p.Pro112Leu

c.335C>T · VCV3490907

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7332 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.7332	likely pathogenic · top 8% in CEP72
REVEL	0.566	indeterminate
SaProt	LLR -14.10	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 7.5	GERP 2.1, phastCons 1
Regional constraint	o/e 1.10	unconstrained · MANE · 41 kb · p 0.005 · regional, not allelic
Overall
CADD	24.8	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CEP72
Protein: p.Pro112Leu
Coding: c.335C>T
MANE Select: NM_018140
Type: single nucleotide variant
Location: chr5:620193 (GRCh38)
Gene constraint: LOEUF 1.409 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 65.74
Residue 112: the lrrct domain

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-pro112leu (accessed [today's date]).

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