Is CEP70 p.Arg165Ter (c.493C>T) pathogenic?

CEP70 p.Arg165Ter (c.493C>T) is classified Uncertain significance in CEP70 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-23). Very rare (popmax 0.00272%, afr).

How common is CEP70 p.Arg165Ter (c.493C>T) in the general population?

CEP70 p.Arg165Ter (c.493C>T) is very rare (popmax 0.00272%, afr) (gnomAD).

CEP70 p.Arg165Ter

c.493C>T · VCV4964457

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00272%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 7 of 18
Splicing
SpliceAI	Δ0.24	acceptor loss · deltas
Pangolin	Δ0.27	loss · gain 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 4.2	GERP 2, phastCons 1
Overall
CADD	37.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00272% African / African-American · 2/73,612 alleles

Filtering AF 0.00158% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00135%

Overall 0.00201% 32/1,595,488 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.00324%	30,872
African / African-Americangrpmax	0.00272%	36,806
European (non-Finnish)	0.0023%	43,467
South Asian	0.00115%	86,766

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Arg165Ter
Coding: c.493C>T
MANE Select: NM_024491
Type: single nucleotide variant
Location: chr3:138537320 (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 p.Arg165Gln Uncertain significance ★ ⚠ same residue
CEP70 p.Arg165Gly Uncertain significance ★ ⚠ same residue
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.Arg189His 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-arg165ter (accessed [today's date]).

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