Is CEP350 p.Leu666= (c.1998A>G) pathogenic?

CEP350 p.Leu666= (c.1998A>G) is classified Likely benign in CEP350 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-01). Very rare (popmax 0.00509%, nfe).

How common is CEP350 p.Leu666= (c.1998A>G) in the general population?

CEP350 p.Leu666= (c.1998A>G) is very rare (popmax 0.00509%, nfe) (gnomAD).

CEP350 p.Leu666=

c.1998A>G · rs371538840 · VCV2639594

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00509%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.81	GERP -1.9, phastCons 0.68
Overall
CADD	5.765	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00509% European (non-Finnish) · 60/1,178,496 alleles

Filtering AF 0.00402% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00362%

Overall 0.00379% 61/1,609,994 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00509%	19,642
Remaining individualsnot grpmax-eligible	0.00161%	62,304

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: CEP350
Protein: p.Leu666=
Coding: c.1998A>G
MANE Select: NM_014810
dbSNP: rs371538840
Type: single nucleotide variant
Location: chr1:180014451 (GRCh38)
Gene constraint: LOEUF 0.402 · pLI 1.00 (gnomAD)

Full CEP350 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CEP350 p.Asp522Gly Benign ★★ same type
CEP350 p.His1462Arg Likely benign ★★ same type
CEP350 p.Ile1905Met Likely benign ★★ same type
CEP350 p.Lys2735Asn Benign ★★ same type
CEP350 c.5567+1G>A Uncertain significance ★ same type
CEP350 p.Ala1096Thr Uncertain significance ★ ⚠ same type
CEP350 p.Ala1160Thr Uncertain significance ★ ⚠ same type
CEP350 p.Ala1163Pro 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/cep350-p-leu666 (accessed [today's date]).

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