Is CEP162 p.Lys1356Arg (c.4067A>G) pathogenic?

CEP162 p.Lys1356Arg (c.4067A>G) is classified Uncertain significance in CEP162 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-10). AlphaMissense: likely benign (0.1123); Very rare (popmax 0.00492%, nfe).

How common is CEP162 p.Lys1356Arg (c.4067A>G) in the general population?

CEP162 p.Lys1356Arg (c.4067A>G) is very rare (popmax 0.00492%, nfe) (gnomAD).

What do computational predictors say about CEP162 p.Lys1356Arg (c.4067A>G)?

AlphaMissense predicts likely benign (score 0.1123) — an in-silico prediction, not a clinical call.

CEP162 p.Lys1356Arg

c.4067A>G · rs1189293341 · VCV2390051

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1123 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00492%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1123	likely benign
REVEL	0.091	moderately benign-leaning
SaProt	LLR -7.69	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 5	GERP 0.72, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 101 kb · p 0.75 · regional, not allelic
Overall
CADD	21.5	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 0.00492% European (non-Finnish) · 58/1,179,712 alleles

Filtering AF 0.00386% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00353%

Overall 0.00372% 60/1,613,556 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00492%	20,340
African / African-American	0.00267%	37,453

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: CEP162
Protein: p.Lys1356Arg
Coding: c.4067A>G
MANE Select: NM_014895
dbSNP: rs1189293341
Type: single nucleotide variant
Location: chr6:84125215 (GRCh38)
Gene constraint: LOEUF 1.101 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 63.93

Full CEP162 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CEP162 p.Leu1052Pro Uncertain significance ★★ ⚠ same type
CEP162 c.687+3A>G Uncertain significance ★ same type
CEP162 p.Ala1224Val Uncertain significance ★ ⚠ same type
CEP162 p.Ala1359Gly Uncertain significance ★ ⚠ same type
CEP162 p.Ala190Thr Uncertain significance ★ ⚠ same type
CEP162 p.Ala375Asp Uncertain significance ★ ⚠ same type
CEP162 p.Ala494Thr Uncertain significance ★ ⚠ same type
CEP162 p.Ala508Val 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/cep162-p-lys1356arg (accessed [today's date]).

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