Is CEP126 p.Arg134Gln (c.401G>A) pathogenic?

CEP126 p.Arg134Gln (c.401G>A) is classified Likely benign in CEP126 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-13). AlphaMissense: likely benign (0.0696); Ultra-rare (popmax 0.0111%, sas).

How common is CEP126 p.Arg134Gln (c.401G>A) in the general population?

CEP126 p.Arg134Gln (c.401G>A) is ultra-rare (popmax 0.0111%, sas) (gnomAD).

What do computational predictors say about CEP126 p.Arg134Gln (c.401G>A)?

AlphaMissense predicts likely benign (score 0.0696) — an in-silico prediction, not a clinical call.

CEP126 p.Arg134Gln

c.401G>A · VCV4225832

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0696 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0111%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0696	likely benign
REVEL	0.026	moderately benign-leaning
SaProt	LLR -6.74	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4	GERP -3.4, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 67 kb · p 0.63 · regional, not allelic
Overall
CADD	4.803	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 0.0111% South Asian · 10/90,132 alleles

Filtering AF 0.006% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00458%

Overall 0.00498% 80/1,605,142 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0111%	9,013
European (non-Finnish)	0.00528%	18,927
Remaining individualsnot grpmax-eligible	0.00483%	20,709
Ashkenazi Jewishnot grpmax-eligible	0.0034%	29,440
East Asian	0.00224%	44,694
Admixed American	0.00167%	59,756
Finnishnot grpmax-eligible	0.00157%	63,786
African / African-American	0.00134%	74,792

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.Arg134Gln
Coding: c.401G>A
MANE Select: NM_020802
Type: single nucleotide variant
Location: chr11:101948037 (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-arg134gln (accessed [today's date]).

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