Is CEP120 p.Thr331Pro (c.991A>C) pathogenic?

CEP120 p.Thr331Pro (c.991A>C) is classified Uncertain significance in CEP120 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-01-07). AlphaMissense: likely pathogenic (0.8349); Very rare (popmax 0.00102%, nfe); Associated with short-rib thoracic dysplasia 13 with or without polydactyly.

What condition is associated with CEP120 p.Thr331Pro (c.991A>C)?

CEP120 p.Thr331Pro (c.991A>C) is associated with short-rib thoracic dysplasia 13 with or without polydactyly (ClinVar).

How common is CEP120 p.Thr331Pro (c.991A>C) in the general population?

CEP120 p.Thr331Pro (c.991A>C) is very rare (popmax 0.00102%, nfe) (gnomAD).

What do computational predictors say about CEP120 p.Thr331Pro (c.991A>C)?

AlphaMissense predicts likely pathogenic (score 0.8349) — an in-silico prediction, not a clinical call.

CEP120 p.Thr331Pro

c.991A>C · rs372144017 · VCV1934942

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8349 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00102%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

short-rib thoracic dysplasia 13 with or without polydactyly

Computational evidence

Protein change
AlphaMissense	0.8349	likely pathogenic
REVEL	0.19	benign-leaning
SaProt	LLR -14.37	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.1	GERP 1.9, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 76 kb · p 0.029 · regional, not allelic
Overall
CADD	25.4	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 0.00102% European (non-Finnish) · 12/1,180,028 alleles

Filtering AF 0.000542% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000428%

Overall 0.000821% 12/1,461,876 alleles · very rare

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.Thr331Pro
Coding: c.991A>C
MANE Select: NM_001375405
dbSNP: rs372144017
Type: single nucleotide variant
Location: chr5:123391157 (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 p.Thr331Ala Uncertain significance ★★ ⚠ same residue
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

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-thr331pro (accessed [today's date]).

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