Is CEP126 p.Pro39Ala (c.115C>G) pathogenic?

CEP126 p.Pro39Ala (c.115C>G) is classified Uncertain significance in CEP126 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-08). AlphaMissense: likely benign (0.0822); Very rare (popmax 0.000424%, nfe).

How common is CEP126 p.Pro39Ala (c.115C>G) in the general population?

CEP126 p.Pro39Ala (c.115C>G) is very rare (popmax 0.000424%, nfe) (gnomAD).

What do computational predictors say about CEP126 p.Pro39Ala (c.115C>G)?

AlphaMissense predicts likely benign (score 0.0822) — an in-silico prediction, not a clinical call.

CEP126 p.Pro39Ala

c.115C>G · rs1255880136 · VCV3142495

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0822 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000424%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0822	likely benign
REVEL	0.037	moderately benign-leaning
SaProt	LLR -6.15	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 1.5	GERP 1.6, phastCons 0.013
Regional constraint	o/e 0.99	unconstrained · MANE · 67 kb · p 0.63 · regional, not allelic
Overall
CADD	19.7	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 0.000424% European (non-Finnish) · 5/1,179,780 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9e-05%

Overall 0.00031% 5/1,613,098 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: CEP126
Protein: p.Pro39Ala
Coding: c.115C>G
MANE Select: NM_178127 · reported on NM_020802
dbSNP: rs1255880136
Type: single nucleotide variant
Location: chr11:101915399 (GRCh38)

Full CEP126 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

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/cep126-p-pro39ala (accessed [today's date]).

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