Is CEP162 p.Leu142Trp (c.425T>G) pathogenic?

CEP162 p.Leu142Trp (c.425T>G) is classified Uncertain significance in CEP162 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-16). AlphaMissense: likely benign (0.2133); Very rare (popmax 0.00238%, nfe).

How common is CEP162 p.Leu142Trp (c.425T>G) in the general population?

CEP162 p.Leu142Trp (c.425T>G) is very rare (popmax 0.00238%, nfe) (gnomAD).

What do computational predictors say about CEP162 p.Leu142Trp (c.425T>G)?

AlphaMissense predicts likely benign (score 0.2133) — an in-silico prediction, not a clinical call.

CEP162 p.Leu142Trp

c.425T>G · rs909879169 · VCV2219575

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2133 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00238%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2133	likely benign
REVEL	0.177	moderately benign-leaning
SaProt	LLR -9.57	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 8.1	GERP 0.68, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 101 kb · p 0.75 · regional, not allelic
Overall
CADD	22.3	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 0.00238% European (non-Finnish) · 28/1,175,494 alleles

Filtering AF 0.00165% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00142%

Overall 0.00174% 28/1,606,370 alleles · very 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: CEP162
Protein: p.Leu142Trp
Coding: c.425T>G
MANE Select: NM_014895
dbSNP: rs909879169
Type: single nucleotide variant
Location: chr6:84215360 (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.Leu142Phe Uncertain significance ★ ⚠ same residue
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

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-leu142trp (accessed [today's date]).

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