Is CEP350 p.Lys1908Glu (c.5722A>G) pathogenic?

CEP350 p.Lys1908Glu (c.5722A>G) is classified Uncertain significance in CEP350 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-09). AlphaMissense: likely benign (0.1256); Ultra-rare (popmax 0.0134%, eas).

How common is CEP350 p.Lys1908Glu (c.5722A>G) in the general population?

CEP350 p.Lys1908Glu (c.5722A>G) is ultra-rare (popmax 0.0134%, eas) (gnomAD).

What do computational predictors say about CEP350 p.Lys1908Glu (c.5722A>G)?

AlphaMissense predicts likely benign (score 0.1256) — an in-silico prediction, not a clinical call.

CEP350 p.Lys1908Glu

c.5722A>G · VCV4000916

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1256 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0134%, eas)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Computational evidence

Protein change
AlphaMissense	0.1256	likely benign
REVEL	0.267	benign-leaning
⇒ AlphaMissense and REVEL both call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.4	GERP 0.9, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 57 kb · p 0.012 · regional, not allelic
Overall
CADD	22.4	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 0.0134% East Asian · 6/44,884 alleles

Filtering AF 0.00579% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00394%

Overall 0.000411% 6/1,461,014 alleles · ultra-rare

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.Lys1908Glu
Coding: c.5722A>G
MANE Select: NM_014810
Type: single nucleotide variant
Location: chr1:180075176 (GRCh38)
Gene constraint: LOEUF 0.402 · pLI 1.00 (gnomAD)
Residue 1908: the 'disordered' region

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-lys1908glu (accessed [today's date]).

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