Is CEP250 p.Ala334Val (c.1001C>T) pathogenic?

CEP250 p.Ala334Val (c.1001C>T) is classified Likely benign in CEP250 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-12-26). AlphaMissense: likely benign (0.1358); Rare (popmax 0.568%, afr).

How common is CEP250 p.Ala334Val (c.1001C>T) in the general population?

CEP250 p.Ala334Val (c.1001C>T) is rare (popmax 0.568%, afr) (gnomAD).

What do computational predictors say about CEP250 p.Ala334Val (c.1001C>T)?

AlphaMissense predicts likely benign (score 0.1358) — an in-silico prediction, not a clinical call.

CEP250 p.Ala334Val

c.1001C>T · rs116166982 · VCV1130123

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.1358 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.568%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1358	likely benign
REVEL	0.022	moderately benign-leaning
SaProt	LLR -6.63	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 1.7	GERP -0.76, phastCons 0.91
Regional constraint	o/e 0.87	unconstrained · MANE · 49 kb · p 4.8e-12 · regional, not allelic
Overall
CADD	21.8	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 0.568% African / African-American · 426/75,020 alleles

Filtering AF 0.523% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.506%

Overall 0.0338% 546/1,613,314 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.568%	176
Remaining individualsnot grpmax-eligible	0.0736%	1,358
Middle Eastern	0.066%	1,515
Admixed American	0.0267%	3,752
European (non-Finnish)	0.00449%	22,250
South Asian	0.0011%	91,068

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.Ala334Val
Coding: c.1001C>T
MANE Select: NM_007186
dbSNP: rs116166982
Type: single nucleotide variant
Location: chr20:35472102 (GRCh38)
Gene constraint: LOEUF 0.86 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 64.68 · 1 PDB
Residue 334: 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.Ala334= Likely benign ★★ 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-ala334val (accessed [today's date]).

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