Is CEP120 p.Pro448= (c.1344A>G) pathogenic?

CEP120 p.Pro448= (c.1344A>G) is classified Likely benign in CEP120 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-28). Very rare (popmax 0.00102%, nfe); Associated with short-rib thoracic dysplasia 13 with or without polydactyly.

What condition is associated with CEP120 p.Pro448= (c.1344A>G)?

CEP120 p.Pro448= (c.1344A>G) is associated with short-rib thoracic dysplasia 13 with or without polydactyly (ClinVar).

How common is CEP120 p.Pro448= (c.1344A>G) in the general population?

CEP120 p.Pro448= (c.1344A>G) is very rare (popmax 0.00102%, nfe) (gnomAD).

CEP120 p.Pro448=

c.1344A>G · rs1423647816 · VCV2794204

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00102%, nfe)

Conditions

short-rib thoracic dysplasia 13 with or without polydactyly

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.71	GERP -3.7, phastCons 0.009
Overall
CADD	5.992	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00102% European (non-Finnish) · 12/1,179,030 alleles

Filtering AF 0.000543% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000429%

Overall 0.000745% 12/1,611,144 alleles · very rare exomes 12/1,458,794 · genomes 0/152,350 · joint denominator

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: CEP120
Protein: p.Pro448=
Coding: c.1344A>G
MANE Select: NM_001375405
dbSNP: rs1423647816
Type: single nucleotide variant
Location: chr5:123388518 (GRCh38)
Gene constraint: LOEUF 0.93 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.22 · 4 PDB
Residue 448: the c2 2 domain

Full CEP120 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

short-rib thoracic dysplasia 13 with or without polydactyly — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CEP120 c.1255+1G>A Likely pathogenic ★★ same condition
CEP120 c.2580+2T>A Likely pathogenic ★★ same condition
CEP120 p.Ala199Pro Pathogenic/Likely pathogenic ★★ same condition
CEP120 p.Arg722Ter Pathogenic/Likely pathogenic ★★ same condition
CEP120 p.Gln775Ter Pathogenic/Likely pathogenic ★★ same condition
CEP120 p.Lys539Ter Pathogenic/Likely pathogenic ★★ same condition
CEP120 c.1038+6T>C Uncertain significance ★★ same condition
CEP120 c.2481+6C>T Uncertain significance ★★ same condition

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/cep120-p-pro448 (accessed [today's date]).

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