Is CEP120 p.Arg340= (c.1018A>C) pathogenic?

CEP120 p.Arg340= (c.1018A>C) is classified Likely benign in CEP120 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-10-28). Ultra-rare (popmax 0.0165%, mid); Associated with short-rib thoracic dysplasia 13 with or without polydactyly.

What condition is associated with CEP120 p.Arg340= (c.1018A>C)?

CEP120 p.Arg340= (c.1018A>C) is associated with short-rib thoracic dysplasia 13 with or without polydactyly (ClinVar).

How common is CEP120 p.Arg340= (c.1018A>C) in the general population?

CEP120 p.Arg340= (c.1018A>C) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

CEP120 p.Arg340=

c.1018A>C · rs375742492 · VCV2708563

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

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 2.9	GERP 0.63, phastCons 1
Overall
CADD	9.879	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0165% Middle Eastern · 1/6,072 alleles

Filtering AF 0.00664% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00616%

Overall 0.00595% 96/1,613,680 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,072
European (non-Finnish)	0.00797%	12,551
Remaining individualsnot grpmax-eligible	0.0016%	62,472

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.Arg340=
Coding: c.1018A>C
MANE Select: NM_001375405
dbSNP: rs375742492
Type: single nucleotide variant
Location: chr5:123391130 (GRCh38)
Gene constraint: LOEUF 0.93 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.22 · 4 PDB

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-arg340 (accessed [today's date]).

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