Is CEP250 p.Arg147Trp (c.439C>T) pathogenic?

CEP250 p.Arg147Trp (c.439C>T) is classified Uncertain significance in CEP250 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-19). AlphaMissense: likely benign (0.1432); Very rare (popmax 0.00535%, afr).

How common is CEP250 p.Arg147Trp (c.439C>T) in the general population?

CEP250 p.Arg147Trp (c.439C>T) is very rare (popmax 0.00535%, afr) (gnomAD).

What do computational predictors say about CEP250 p.Arg147Trp (c.439C>T)?

AlphaMissense predicts likely benign (score 0.1432) — an in-silico prediction, not a clinical call.

CEP250 p.Arg147Trp

c.439C>T · rs941233169 · VCV1064320

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1432 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00535%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1432	likely benign
REVEL	0.234	benign-leaning
SaProt	LLR -7.28	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 3.3	GERP 2.5, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 49 kb · p 4.8e-12 · regional, not allelic
Overall
CADD	33.0	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 0.00535% African / African-American · 4/74,798 alleles

Filtering AF 0.00175% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.00167% 27/1,612,218 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00535%	18,699
Admixed American	0.00501%	19,947
East Asian	0.00223%	44,834
European (non-Finnish)	0.00153%	65,507
South Asian	0.0011%	90,772

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: CEP250
Protein: p.Arg147Trp
Coding: c.439C>T
MANE Select: NM_007186
dbSNP: rs941233169
Type: single nucleotide variant
Location: chr20:35466151 (GRCh38)
Gene constraint: LOEUF 0.86 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 64.68 · 1 PDB
Residue 147: a UniProt-annotated variant site (in crdhl2)

Full CEP250 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CEP250 p.Arg147Gln Uncertain significance ★ ⚠ same residue
CEP250 p.Arg147fs Pathogenic ★ same residue
CEP250 p.Arg1045Ter Pathogenic/Likely pathogenic ★★ same type
CEP250 p.Arg1155Ter Pathogenic/Likely pathogenic ★★ same type
CEP250 p.Arg1336Ter Pathogenic/Likely pathogenic ★★ same type
CEP250 p.Arg1343Ter Pathogenic/Likely pathogenic ★★ same type
CEP250 p.Arg1499Ter Pathogenic/Likely pathogenic ★★ same type
CEP250 p.Arg1695Ter Pathogenic/Likely pathogenic ★★ 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/cep250-p-arg147trp (accessed [today's date]).

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