Is CEP192 p.Ser290Phe (c.869C>T) pathogenic?

CEP192 p.Ser290Phe (c.869C>T) is classified Uncertain significance in CEP192 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-06-18). AlphaMissense: likely benign (0.1599); Very rare (popmax 7.2e-05%).

How common is CEP192 p.Ser290Phe (c.869C>T) in the general population?

CEP192 p.Ser290Phe (c.869C>T) is very rare (popmax 7.2e-05%) (gnomAD).

What do computational predictors say about CEP192 p.Ser290Phe (c.869C>T)?

AlphaMissense predicts likely benign (score 0.1599) — an in-silico prediction, not a clinical call.

CEP192 p.Ser290Phe

c.869C>T · rs1461696279 · VCV2233409

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1599 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 7.2e-05%)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1599	likely benign
REVEL	0.045	moderately benign-leaning
SaProt	LLR -7.83	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 -0.56	GERP 1.8
Regional constraint	o/e 0.96	unconstrained · MANE · 125 kb · p 0.044 · regional, not allelic
Overall
CADD	21.0	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 7.2e-05%

Overall 7.2e-05% 1/1,389,838 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: CEP192
Protein: p.Ser290Phe
Coding: c.869C>T
MANE Select: NM_032142
dbSNP: rs1461696279
Type: single nucleotide variant
Location: chr18:13018559 (GRCh38)
Gene constraint: LOEUF 0.61 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 51.37 · 6 PDB
Residue 290: the 'disordered' region

Full CEP192 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CEP192 p.Ala2312Val Uncertain significance ★★ ⚠ same type
CEP192 p.Gly37Val Uncertain significance ★★ same type
CEP192 p.Asn1883Ser Benign ★★ same type
CEP192 p.Gly1571= Benign ★★ same type
CEP192 p.Leu111Phe Benign ★★ same type
CEP192 p.Pro1159Arg Benign ★★ same type
CEP192 p.Pro613= Benign ★★ same type
CEP192 p.Thr1053Ala Benign ★★ 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/cep192-p-ser290phe (accessed [today's date]).

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