Is CEP70 p.His294Arg (c.881A>G) pathogenic?

CEP70 p.His294Arg (c.881A>G) is classified Uncertain significance in CEP70 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-20). AlphaMissense: likely benign (0.1131); Ultra-rare (popmax 0.0682%, nfe).

How common is CEP70 p.His294Arg (c.881A>G) in the general population?

CEP70 p.His294Arg (c.881A>G) is ultra-rare (popmax 0.0682%, nfe) (gnomAD).

What do computational predictors say about CEP70 p.His294Arg (c.881A>G)?

AlphaMissense predicts likely benign (score 0.1131) — an in-silico prediction, not a clinical call.

CEP70 p.His294Arg

c.881A>G · rs200516983 · VCV3143022

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1131 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0682%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1131	likely benign
REVEL	0.059	moderately benign-leaning
SaProt	LLR -5.27	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 3.3	GERP 1.1, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 78 kb · p 0.42 · regional, not allelic
Overall
CADD	18.49	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 0.0682% European (non-Finnish) · 726/1,064,076 alleles

Filtering AF 0.0641% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0624%

Overall 0.0572% 802/1,401,494 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0682%	1,466
South Asian	0.0495%	2,022
African / African-American	0.0338%	2,956
Remaining individualsnot grpmax-eligible	0.0324%	3,082
Admixed American	0.0233%	4,293
Middle Eastern	0.019%	5,270

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: CEP70
Protein: p.His294Arg
Coding: c.881A>G
MANE Select: NM_024491
dbSNP: rs200516983
Type: single nucleotide variant
Location: chr3:138525553 (GRCh38)
Gene constraint: LOEUF 1.077 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.91

Full CEP70 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CEP70 c.1732+103G>C Uncertain significance ★ same type
CEP70 p.Ala198Val Uncertain significance ★ ⚠ same type
CEP70 p.Ala251Thr Uncertain significance ★ ⚠ same type
CEP70 p.Ala588Ser Uncertain significance ★ ⚠ same type
CEP70 p.Ala5Pro Uncertain significance ★ ⚠ same type
CEP70 p.Arg165Gln Uncertain significance ★ ⚠ same type
CEP70 p.Arg165Gly Uncertain significance ★ ⚠ same type
CEP70 p.Arg165Ter 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/cep70-p-his294arg (accessed [today's date]).

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