Is CEP192 p.Ser1316Pro (c.3946T>C) pathogenic?

CEP192 p.Ser1316Pro (c.3946T>C) is classified Likely benign in CEP192 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-15). AlphaMissense: likely benign (0.0485); Absent from gnomAD v4.1.

How common is CEP192 p.Ser1316Pro (c.3946T>C) in the general population?

CEP192 p.Ser1316Pro (c.3946T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CEP192 p.Ser1316Pro (c.3946T>C)?

AlphaMissense predicts likely benign (score 0.0485) — an in-silico prediction, not a clinical call.

CEP192 p.Ser1316Pro

c.3946T>C · VCV4226110

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0485 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0485	likely benign
REVEL	0.047	moderately benign-leaning
SaProt	LLR -7.15	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 1.7	GERP 0.44, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 125 kb · p 0.044 · regional, not allelic
Overall
CADD	7.504	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CEP192
Protein: p.Ser1316Pro
Coding: c.3946T>C
MANE Select: NM_032142
Type: single nucleotide variant
Location: chr18:13056536 (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.Ser1316Thr Uncertain significance ★ ⚠ same residue
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

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-ser1316pro (accessed [today's date]).

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