Is CEP70 p.His39Arg (c.116A>G) pathogenic?

CEP70 p.His39Arg (c.116A>G) is classified Uncertain significance in CEP70 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-04). AlphaMissense: likely benign (0.0838); Very rare (popmax 0.0067%, eas).

How common is CEP70 p.His39Arg (c.116A>G) in the general population?

CEP70 p.His39Arg (c.116A>G) is very rare (popmax 0.0067%, eas) (gnomAD).

What do computational predictors say about CEP70 p.His39Arg (c.116A>G)?

AlphaMissense predicts likely benign (score 0.0838) — an in-silico prediction, not a clinical call.

CEP70 p.His39Arg

c.116A>G · VCV3490897

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0838 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0067%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0838	likely benign
REVEL	0.049	moderately benign-leaning
SaProt	LLR -6.67	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 0.81	GERP 1.1, phastCons 0.97
Regional constraint	o/e 0.97	unconstrained · MANE · 78 kb · p 0.42 · regional, not allelic
Overall
CADD	15.93	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 0.0067% East Asian · 3/44,744 alleles

Filtering AF 0.00178% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000893%

Overall 0.000343% 5/1,459,692 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0067%	14,915
European (non-Finnish)	0.00017%	589,518

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.His39Arg
Coding: c.116A>G
MANE Select: NM_024491
Type: single nucleotide variant
Location: chr3:138571310 (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-his39arg (accessed [today's date]).

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