Is CEP135 p.Pro31Arg (c.92C>G) pathogenic?

CEP135 p.Pro31Arg (c.92C>G) is classified Uncertain significance in CEP135 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-04-29). AlphaMissense: likely pathogenic (0.6953); Absent from gnomAD v4.1.

How common is CEP135 p.Pro31Arg (c.92C>G) in the general population?

CEP135 p.Pro31Arg (c.92C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CEP135 p.Pro31Arg (c.92C>G)?

AlphaMissense predicts likely pathogenic (score 0.6953) — an in-silico prediction, not a clinical call.

CEP135 p.Pro31Arg

c.92C>G · rs2476003156 · VCV2131766

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6953 · 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	0.6953	likely pathogenic · top 10% in CEP135
REVEL	0.627	indeterminate
SaProt	LLR -13.49	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 7.6	GERP 1.5, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 72 kb · p 0.83 · regional, not allelic
Overall
CADD	26.5	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

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: CEP135
Protein: p.Pro31Arg
Coding: c.92C>G
MANE Select: NM_025009
dbSNP: rs2476003156
Type: single nucleotide variant
Location: chr4:55952222 (GRCh38)
Gene constraint: LOEUF 0.989 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.15 · 2 PDB
Residue 31: the 'homodimerization' region

Full CEP135 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CEP135 c.473-1G>C Likely pathogenic ★★ same type
CEP135 p.Arg1083Ter Pathogenic/Likely pathogenic ★★ same type
CEP135 p.Arg292Ter Pathogenic/Likely pathogenic ★★ same type
CEP135 p.Arg418Ter Pathogenic ★★ same type
CEP135 p.Arg470Ter Pathogenic/Likely pathogenic ★★ same type
CEP135 p.Arg908Ter Pathogenic ★★ same type
CEP135 p.Leu578Ter Pathogenic ★★ same type
CEP135 p.Lys1071Ter Pathogenic/Likely pathogenic ★★ 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/cep135-p-pro31arg (accessed [today's date]).

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