Is CEP192 p.Asp878Val (c.2633A>T) pathogenic?

CEP192 p.Asp878Val (c.2633A>T) is classified Uncertain significance in CEP192 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-10). AlphaMissense: likely benign (0.1776); Ultra-rare (popmax 0.0253%, sas).

How common is CEP192 p.Asp878Val (c.2633A>T) in the general population?

CEP192 p.Asp878Val (c.2633A>T) is ultra-rare (popmax 0.0253%, sas) (gnomAD).

What do computational predictors say about CEP192 p.Asp878Val (c.2633A>T)?

AlphaMissense predicts likely benign (score 0.1776) — an in-silico prediction, not a clinical call.

CEP192 p.Asp878Val

c.2633A>T · VCV3490674

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1776 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0253%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1776	likely benign
REVEL	0.274	benign-leaning
SaProt	LLR -7.36	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 0.42	GERP -3.9
Regional constraint	o/e 0.96	unconstrained · MANE · 125 kb · p 0.044 · regional, not allelic
Overall
CADD	10.68	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 0.0253% South Asian · 23/91,082 alleles

Filtering AF 0.0172% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0146%

Overall 0.0018% 29/1,614,064 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0253%	3,960
Remaining individualsnot grpmax-eligible	0.0064%	15,622
East Asian	0.00446%	22,445

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.Asp878Val
Coding: c.2633A>T
MANE Select: NM_032142
Type: single nucleotide variant
Location: chr18:13049424 (GRCh38)
Gene constraint: LOEUF 0.61 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 51.37 · 6 PDB

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-asp878val (accessed [today's date]).

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