Is CEP120 p.Pro394Ser (c.1180C>T) pathogenic?

CEP120 p.Pro394Ser (c.1180C>T) is classified Conflicting classifications of pathogenicity in CEP120 (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2024-11-13). AlphaMissense: likely benign (0.114); Rare (popmax 0.136%, nfe); Associated with Inborn genetic diseases.

What condition is associated with CEP120 p.Pro394Ser (c.1180C>T)?

CEP120 p.Pro394Ser (c.1180C>T) is associated with Inborn genetic diseases, short-rib thoracic dysplasia 13 with or without polydactyly (ClinVar).

How common is CEP120 p.Pro394Ser (c.1180C>T) in the general population?

CEP120 p.Pro394Ser (c.1180C>T) is rare (popmax 0.136%, nfe) (gnomAD).

What do computational predictors say about CEP120 p.Pro394Ser (c.1180C>T)?

AlphaMissense predicts likely benign (score 0.114) — an in-silico prediction, not a clinical call.

CEP120 p.Pro394Ser

c.1180C>T · rs200450605 · VCV642185

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.114 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.136%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.114	likely benign
REVEL	0.058	moderately benign-leaning
SaProt	LLR -5.40	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 8.7	GERP 1.6, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 76 kb · p 0.029 · regional, not allelic
Overall
CADD	19.25	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 0.136% European (non-Finnish) · 1,608/1,180,026 alleles

Filtering AF 0.131% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.128%

Overall 0.105% 1,702/1,613,930 alleles · rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.136%	734
Remaining individualsnot grpmax-eligible	0.101%	992
Finnishnot grpmax-eligible	0.025%	4,000
African / African-American	0.0174%	5,760
Middle Eastern	0.0164%	6,082
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,602

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.Pro394Ser
Coding: c.1180C>T
MANE Select: NM_001375405
dbSNP: rs200450605
Type: single nucleotide variant
Location: chr5:123389999 (GRCh38)
Gene constraint: LOEUF 0.93 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.22 · 4 PDB
Residue 394: the 'disordered' region

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: short-rib thoracic dysplasia 13 with or without polydactyly

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-pro394ser (accessed [today's date]).

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