Is CEP164 p.Gln876Arg (c.2627A>G) pathogenic?

CEP164 p.Gln876Arg (c.2627A>G) is classified Uncertain significance in CEP164 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2024-08-30). AlphaMissense: likely benign (0.2171); Ultra-rare (popmax 0.0698%, sas); Associated with Inborn genetic diseases.

What condition is associated with CEP164 p.Gln876Arg (c.2627A>G)?

CEP164 p.Gln876Arg (c.2627A>G) is associated with Inborn genetic diseases, nephronophthisis 15 (ClinVar).

How common is CEP164 p.Gln876Arg (c.2627A>G) in the general population?

CEP164 p.Gln876Arg (c.2627A>G) is ultra-rare (popmax 0.0698%, sas) (gnomAD).

What do computational predictors say about CEP164 p.Gln876Arg (c.2627A>G)?

AlphaMissense predicts likely benign (score 0.2171) — an in-silico prediction, not a clinical call.

CEP164 p.Gln876Arg

c.2627A>G · rs752659513 · VCV1035241

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.2171 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0698%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2171	likely benign
REVEL	0.132	moderately benign-leaning
SaProt	LLR -5.38	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 7	GERP 1.2, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 74 kb · p 0.19 · regional, not allelic
Overall
CADD	21.2	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 0.0698% South Asian · 62/88,852 alleles

Filtering AF 0.0558% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0508%

Overall 0.00443% 71/1,600,960 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0698%	1,433
Middle Eastern	0.0165%	6,044
Remaining individualsnot grpmax-eligible	0.00644%	15,518
African / African-American	0.00134%	74,832
European (non-Finnish)	0.000255%	391,431

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: CEP164
Protein: p.Gln876Arg
Coding: c.2627A>G
MANE Select: NM_014956
dbSNP: rs752659513
Type: single nucleotide variant
Location: chr11:117394360 (GRCh38)
Gene constraint: LOEUF 1.009 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 63.08 · 4 PDB

Full CEP164 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: nephronophthisis 15

Similar variants

CEP164 c.1234-2A>T Likely pathogenic ★★ same condition
CEP164 c.1724+1G>A Likely pathogenic ★★ same condition
CEP164 c.1934+1G>A Likely pathogenic ★★ same condition
CEP164 c.2361+1G>A Likely pathogenic ★★ same condition
CEP164 c.2493+1G>A Likely pathogenic ★★ same condition
CEP164 c.2914-1G>C Likely pathogenic ★★ same condition
CEP164 c.3748+2T>C Likely pathogenic ★★ same condition
CEP164 c.3749-2A>G Likely pathogenic ★★ same condition

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/cep164-p-gln876arg (accessed [today's date]).

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