Is CEP250 p.Arg397Gln (c.1190G>A) pathogenic?

CEP250 p.Arg397Gln (c.1190G>A) is classified Conflicting classifications of pathogenicity in CEP250 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2022-09-29). AlphaMissense: likely benign (0.0674); Very rare (popmax 0.00333%, amr).

How common is CEP250 p.Arg397Gln (c.1190G>A) in the general population?

CEP250 p.Arg397Gln (c.1190G>A) is very rare (popmax 0.00333%, amr) (gnomAD).

What do computational predictors say about CEP250 p.Arg397Gln (c.1190G>A)?

AlphaMissense predicts likely benign (score 0.0674) — an in-silico prediction, not a clinical call.

CEP250 p.Arg397Gln

c.1190G>A · rs766701871 · VCV968418

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0674 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00333%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0674	likely benign
REVEL	0.075	moderately benign-leaning
SaProt	LLR -5.58	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 -1.3	GERP -5
Regional constraint	o/e 0.87	unconstrained · MANE · 49 kb · p 4.8e-12 · regional, not allelic
Overall
CADD	12.51	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

Grpmax group 0.00333% Admixed American · 2/59,996 alleles

Filtering AF 0.000553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000366%

Overall 0.00105% 17/1,613,978 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00333%	29,998
Remaining individualsnot grpmax-eligible	0.0032%	31,241
East Asian	0.00223%	44,894
African / African-American	0.00134%	74,904
European (non-Finnish)	0.000932%	107,275

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.Arg397Gln
Coding: c.1190G>A
MANE Select: NM_007186
dbSNP: rs766701871
Type: single nucleotide variant
Location: chr20:35472812 (GRCh38)
Gene constraint: LOEUF 0.86 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 64.68 · 1 PDB
Residue 397: a UniProt-annotated variant site (in crdhl2); a UniProt-annotated variant site (in crdhl2; also found in a family with non-syndromic retinitis pigmentosa)

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

Similar variants

CEP250 p.Arg397Trp Uncertain significance ★★ ⚠ 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
CEP250 p.Arg1869Ter 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-arg397gln (accessed [today's date]).

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