Is CEP250 p.Val613Phe (c.1837G>T) pathogenic?

CEP250 p.Val613Phe (c.1837G>T) is classified Benign in CEP250 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-02-02). AlphaMissense: ambiguous (0.3527); Common (popmax 6.52%, afr) — too common for a highly-penetrant pathogenic allele.

What do computational predictors say about CEP250 p.Val613Phe (c.1837G>T)?

AlphaMissense predicts ambiguous (score 0.3527) — an in-silico prediction, not a clinical call.

CEP250 p.Val613Phe

Q: How common is CEP250 p.Val613Phe (c.1837G>T) in the general population?

CEP250 p.Val613Phe (c.1837G>T) is common (popmax 6.52%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1837G>T · rs74929920 · VCV714815

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

ambiguous

0.3527 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 6.52%, afr) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3527	ambiguous
REVEL	0.29	benign-leaning
SaProt	LLR -8.84	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.3	GERP -0.2, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 49 kb · p 4.8e-12 · regional, not allelic
Overall
CADD	23.4	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 6.52% African / African-American · 4,890/75,022 alleles

Filtering AF 6.37% ClinGen BA1/BS1 input FAF95, joint · FAF99 6.3%

Overall 0.344% 5,552/1,613,586 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	6.52%	15
Middle Eastern	0.528%	189
Remaining individualsnot grpmax-eligible	0.466%	215
Admixed American	0.373%	268
South Asian	0.0154%	6,506
European (non-Finnish)	0.00848%	11,795
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: CEP250
Protein: p.Val613Phe
Coding: c.1837G>T
MANE Select: NM_007186
dbSNP: rs74929920
Type: single nucleotide variant
Location: chr20:35476569 (GRCh38)
Gene constraint: LOEUF 0.86 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 64.68 · 1 PDB
Residue 613: 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.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
CEP250 p.Arg188Ter 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-val613phe (accessed [today's date]).

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