Is CEP164 p.Arg93Trp (c.277C>T) pathogenic?

CEP164 p.Arg93Trp (c.277C>T) is classified Pathogenic/Likely pathogenic in CEP164 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-08-21). AlphaMissense: likely pathogenic (0.7819); Very rare (popmax 0.00669%, eas); Associated with CEP164-related disorder.

What condition is associated with CEP164 p.Arg93Trp (c.277C>T)?

CEP164 p.Arg93Trp (c.277C>T) is associated with CEP164-related disorder, nephronophthisis 15 (ClinVar).

How common is CEP164 p.Arg93Trp (c.277C>T) in the general population?

CEP164 p.Arg93Trp (c.277C>T) is very rare (popmax 0.00669%, eas) (gnomAD).

What do computational predictors say about CEP164 p.Arg93Trp (c.277C>T)?

AlphaMissense predicts likely pathogenic (score 0.7819) — an in-silico prediction, not a clinical call.

CEP164 p.Arg93Trp

c.277C>T · rs387907310 · VCV37296

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

AlphaMissense

likely pathogenic

0.7819 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00669%, eas)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

CEP164-related disorder

Computational evidence

Protein change
AlphaMissense	0.7819	likely pathogenic ✓ concordant with ClinVar · top 5% in CEP164
REVEL	0.624	indeterminate
SaProt	LLR -11.69	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 1.7, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 74 kb · p 0.19 · regional, not allelic
Overall
CADD	32.0	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 0.00669% East Asian · 3/44,868 alleles

Filtering AF 0.00207% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00183%

Overall 0.0026% 42/1,613,532 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00669%	14,956
South Asian	0.00329%	30,355
Remaining individualsnot grpmax-eligible	0.0032%	31,240
European (non-Finnish)	0.00288%	34,705

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.Arg93Trp
Coding: c.277C>T
MANE Select: NM_014956
dbSNP: rs387907310
Type: single nucleotide variant
Location: chr11:117351872 (GRCh38)
Gene constraint: LOEUF 1.009 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 63.08 · 4 PDB
Residue 93: the 'interaction with atrip' region; a UniProt-annotated variant site (in nphp15); an α-helix

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

Disease context

CEP164-related disorder

Also linked: nephronophthisis 15

Similar variants

CEP164 p.Arg93Gln Uncertain significance ★★ ⚠ 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-arg93trp (accessed [today's date]).

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