Is CEP164 p.Arg7Cys (c.19C>T) pathogenic?

CEP164 p.Arg7Cys (c.19C>T) is classified Uncertain significance in CEP164 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-14). AlphaMissense: likely benign (0.0974); Very rare (popmax 0.0022%, sas); Associated with Inborn genetic diseases.

What condition is associated with CEP164 p.Arg7Cys (c.19C>T)?

CEP164 p.Arg7Cys (c.19C>T) is associated with Inborn genetic diseases (ClinVar).

How common is CEP164 p.Arg7Cys (c.19C>T) in the general population?

CEP164 p.Arg7Cys (c.19C>T) is very rare (popmax 0.0022%, sas) (gnomAD).

What do computational predictors say about CEP164 p.Arg7Cys (c.19C>T)?

AlphaMissense predicts likely benign (score 0.0974) — an in-silico prediction, not a clinical call.

CEP164 p.Arg7Cys

c.19C>T · VCV4225999

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0974 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0022%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0974	likely benign
REVEL	0.125	moderately benign-leaning
SaProt	LLR -9.34	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 1.8	GERP -2.6, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 74 kb · p 0.19 · regional, not allelic
Overall
CADD	18.65	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 0.0022% South Asian · 2/91,076 alleles

Filtering AF 0.000365% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000137%

Overall 0.000434% 7/1,613,920 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0022%	45,538
Admixed American	0.00167%	59,990
African / African-American	0.00134%	74,880
European (non-Finnish)	0.000254%	393,323

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.Arg7Cys
Coding: c.19C>T
MANE Select: NM_014956
Type: single nucleotide variant
Location: chr11:117338605 (GRCh38)
Gene constraint: LOEUF 1.009 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 63.08 · 4 PDB
Residue 7: the 'interaction with atrip' region; a β-strand

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

Similar variants

CEP164 p.Arg7His Uncertain significance ★★ ⚠ same residue
CEP164 c.3089+6G>A Uncertain significance ★★ same condition
CEP164 p.Ala1105Val Uncertain significance ★★ ⚠ same condition
CEP164 p.Ala1145Val Uncertain significance ★★ ⚠ same condition
CEP164 p.Ala952Thr Uncertain significance ★★ ⚠ same condition
CEP164 p.Arg1122Pro Uncertain significance ★★ ⚠ same condition
CEP164 p.Arg1125Trp Uncertain significance ★★ ⚠ same condition
CEP164 p.Arg1139Leu Uncertain significance ★★ ⚠ 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-arg7cys (accessed [today's date]).

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