Is CEP250 p.Ala976Ser (c.2926G>T) pathogenic?

CEP250 p.Ala976Ser (c.2926G>T) is classified Uncertain significance in CEP250 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-30). AlphaMissense: likely benign (0.1106); Absent from gnomAD v4.1.

How common is CEP250 p.Ala976Ser (c.2926G>T) in the general population?

CEP250 p.Ala976Ser (c.2926G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CEP250 p.Ala976Ser (c.2926G>T)?

AlphaMissense predicts likely benign (score 0.1106) — an in-silico prediction, not a clinical call.

CEP250 p.Ala976Ser

c.2926G>T · rs1319120324 · VCV2299590

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1106 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1106	likely benign
REVEL	0.065	moderately benign-leaning
SaProt	LLR -7.62	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 4.3	GERP -0.29, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 49 kb · p 4.8e-12 · regional, not allelic
Overall
CADD	15.93	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

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: CEP250
Protein: p.Ala976Ser
Coding: c.2926G>T
MANE Select: NM_007186
dbSNP: rs1319120324
Type: single nucleotide variant
Location: chr20:35493465 (GRCh38)
Gene constraint: LOEUF 0.86 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 64.68 · 1 PDB
Residue 976: 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

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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-ala976ser (accessed [today's date]).

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