Is CEP164 p.His477Arg (c.1430A>G) pathogenic?

CEP164 p.His477Arg (c.1430A>G) is classified Benign in CEP164 (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-02-03). AlphaMissense: likely benign (0.0643); Common (popmax 5.38%, mid) — too common for a highly-penetrant pathogenic allele; Associated with nephronophthisis 15.

What condition is associated with CEP164 p.His477Arg (c.1430A>G)?

CEP164 p.His477Arg (c.1430A>G) is associated with nephronophthisis 15 (ClinVar).

How is Senior-Loken syndrome inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about CEP164 p.His477Arg (c.1430A>G)?

AlphaMissense predicts likely benign (score 0.0643) — an in-silico prediction, not a clinical call.

CEP164 p.His477Arg

Q: How common is CEP164 p.His477Arg (c.1430A>G) in the general population?

CEP164 p.His477Arg (c.1430A>G) is common (popmax 5.38%, mid) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1430A>G · rs117083334 · VCV194251

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

AlphaMissense

likely benign

0.0643 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 5.38%, mid) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

nephronophthisis 15

Computational evidence

Protein change
AlphaMissense	0.0643	likely benign
REVEL	0.02	moderately benign-leaning
SaProt	LLR -4.72	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.21	acceptor loss, 5 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP -5.3	GERP -0.88
Regional constraint	o/e 0.97	unconstrained · MANE · 74 kb · p 0.19 · regional, not allelic
Overall
CADD	0.002	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 5.38% Middle Eastern · 316/5,872 alleles

Filtering AF 4.89% ClinGen BA1/BS1 input FAF95, joint · FAF99 4.7%

Overall 3.3% 53,172/1,609,834 alleles · common

Ancestry group	Frequency	1 in
Middle Easterngrpmax	5.38%	19
Ashkenazi Jewishnot grpmax-eligible	4.58%	22
European (non-Finnish)	3.84%	26
Remaining individualsnot grpmax-eligible	3.41%	29
Amishnot grpmax-eligible	2.42%	41
Admixed American	2.33%	43
Finnishnot grpmax-eligible	2.12%	47
South Asian	1%	100
African / African-American	0.679%	147
East Asian	0.00446%	22,397

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.His477Arg
Coding: c.1430A>G
MANE Select: NM_014956
dbSNP: rs117083334
Type: single nucleotide variant
Location: chr11:117381721 (GRCh38)
Gene constraint: LOEUF 1.009 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 63.08 · 4 PDB
Residue 477: the 'disordered' region

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

Disease context

nephronophthisis 15 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Senior-Loken syndrome (Orphanet):

Inheritance: Autosomal recessive
Onset: Adolescent, Adult, Childhood, Infancy
Prevalence: 1-9 / 1 000 000 (Worldwide)

Similar variants

CEP164 p.His477= Likely benign ★★ same residue
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

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-his477arg (accessed [today's date]).

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