Is CEP192 p.Ser2250Phe (c.6749C>T) pathogenic?

CEP192 p.Ser2250Phe (c.6749C>T) is classified Uncertain significance in CEP192 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-07). AlphaMissense: likely benign (0.1101); Very rare (popmax 0.0017%, nfe).

How common is CEP192 p.Ser2250Phe (c.6749C>T) in the general population?

CEP192 p.Ser2250Phe (c.6749C>T) is very rare (popmax 0.0017%, nfe) (gnomAD).

What do computational predictors say about CEP192 p.Ser2250Phe (c.6749C>T)?

AlphaMissense predicts likely benign (score 0.1101) — an in-silico prediction, not a clinical call.

CEP192 p.Ser2250Phe

c.6749C>T · VCV4000822

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1101 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0017%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1101	likely benign
REVEL	0.051	moderately benign-leaning
SaProt	LLR -8.67	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.33 · evaluated, not missing
Constraint at this position
Conservation	phyloP 0.16	GERP -1.3
Regional constraint	o/e 0.96	unconstrained · MANE · 125 kb · p 0.044 · regional, not allelic
Overall
CADD	13.55	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 0.0017% European (non-Finnish) · 20/1,179,778 alleles

Filtering AF 0.00111% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0009%

Overall 0.00144% 21/1,461,574 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0017%	58,989
Finnishnot grpmax-eligible	0.00156%	64,028

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.Ser2250Phe
Coding: c.6749C>T
MANE Select: NM_032142
Type: single nucleotide variant
Location: chr18:13100390 (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-ser2250phe (accessed [today's date]).

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