Is CEP126 p.Arg72His (c.215G>A) pathogenic?

CEP126 p.Arg72His (c.215G>A) is classified Uncertain significance in CEP126 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-05). AlphaMissense: likely benign (0.2584); Rare (popmax 0.17%, eas).

How common is CEP126 p.Arg72His (c.215G>A) in the general population?

CEP126 p.Arg72His (c.215G>A) is rare (popmax 0.17%, eas) (gnomAD).

What do computational predictors say about CEP126 p.Arg72His (c.215G>A)?

AlphaMissense predicts likely benign (score 0.2584) — an in-silico prediction, not a clinical call.

CEP126 p.Arg72His

c.215G>A · rs78220060 · VCV3142503

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2584 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.17%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2584	likely benign
REVEL	0.13	moderately benign-leaning
SaProt	LLR -6.98	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 6.6	GERP 2.2, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 67 kb · p 0.63 · regional, not allelic
Overall
CADD	25.2	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 0.17% East Asian · 76/44,788 alleles

Filtering AF 0.139% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.128%

Overall 0.00688% 111/1,612,430 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.17%	589
Admixed American	0.0317%	3,156
Remaining individualsnot grpmax-eligible	0.00641%	15,604
South Asian	0.00439%	22,762
African / African-American	0.00133%	74,976
European (non-Finnish)	0.000594%	168,406

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.Arg72His
Coding: c.215G>A
MANE Select: NM_020802
dbSNP: rs78220060
Type: single nucleotide variant
Location: chr11:101922727 (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-arg72his (accessed [today's date]).

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