Is CEP120 p.Ala57= (c.171T>C) pathogenic?

CEP120 p.Ala57= (c.171T>C) is classified Likely benign in CEP120 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-10-04). Ultra-rare (popmax 0.0839%, sas); Associated with short-rib thoracic dysplasia 13 with or without polydactyly.

What condition is associated with CEP120 p.Ala57= (c.171T>C)?

CEP120 p.Ala57= (c.171T>C) is associated with short-rib thoracic dysplasia 13 with or without polydactyly (ClinVar).

How common is CEP120 p.Ala57= (c.171T>C) in the general population?

CEP120 p.Ala57= (c.171T>C) is ultra-rare (popmax 0.0839%, sas) (gnomAD).

CEP120 p.Ala57=

c.171T>C · rs571743687 · VCV2158480

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0839%, sas)

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	GERP -2.3, phastCons 1
Overall
CADD	10.67	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0839% South Asian · 76/90,606 alleles

Filtering AF 0.0687% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0631%

Overall 0.00515% 83/1,610,574 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0839%	1,192
Remaining individualsnot grpmax-eligible	0.00964%	10,378
European (non-Finnish)	8.49e-05%	1,177,736

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.Ala57=
Coding: c.171T>C
MANE Select: NM_001375405
dbSNP: rs571743687
Type: single nucleotide variant
Location: chr5:123418394 (GRCh38)
Gene constraint: LOEUF 0.93 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.22 · 4 PDB
Residue 57: the c2 1 domain; a β-strand

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-ala57 (accessed [today's date]).

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