Is CEP126 p.Pro1031Leu (c.3092C>T) pathogenic?

CEP126 p.Pro1031Leu (c.3092C>T) is classified Uncertain significance in CEP126 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-06). AlphaMissense: likely benign (0.1341); Rare (popmax 0.103%, sas).

How common is CEP126 p.Pro1031Leu (c.3092C>T) in the general population?

CEP126 p.Pro1031Leu (c.3092C>T) is rare (popmax 0.103%, sas) (gnomAD).

What do computational predictors say about CEP126 p.Pro1031Leu (c.3092C>T)?

AlphaMissense predicts likely benign (score 0.1341) — an in-silico prediction, not a clinical call.

CEP126 p.Pro1031Leu

c.3092C>T · rs369407746 · VCV3142514

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1341 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.103%, sas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1341	likely benign
REVEL	0.148	moderately benign-leaning
SaProt	LLR -10.35	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP 1.8, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 11 kb · p 0.15 · regional, not allelic
Overall
CADD	22.2	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 0.103% South Asian · 94/91,064 alleles

Filtering AF 0.0863% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0801%

Overall 0.00744% 120/1,613,758 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.103%	969
Middle Eastern	0.0165%	6,054
African / African-American	0.012%	8,333
Remaining individualsnot grpmax-eligible	0.0064%	15,622
East Asian	0.00446%	22,397
Admixed American	0.00167%	60,016
European (non-Finnish)	0.000763%	131,094

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.Pro1031Leu
Coding: c.3092C>T
MANE Select: NM_020802
dbSNP: rs369407746
Type: single nucleotide variant
Location: chr11:101986889 (GRCh38)
Gene constraint: LOEUF 0.732 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 49.44

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

Similar variants

CEP126 p.Gln146Glu Benign ★★ same type
CEP126 p.His308Leu Benign ★★ same type
CEP126 p.Leu226= Benign ★★ same type
CEP126 p.Met1021Thr Benign ★★ same type
CEP126 p.Pro710Ser Benign ★★ same type
CEP126 p.Ser372Pro Benign ★★ same type
CEP126 p.Ala1028Thr Uncertain significance ★ ⚠ same type
CEP126 p.Ala460Val 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/cep126-p-pro1031leu (accessed [today's date]).

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