Is COMP p.Pro156= (c.468G>T) pathogenic?

COMP p.Pro156= (c.468G>T) is classified Benign/Likely benign in COMP (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-01-04). Rare (popmax 0.488%, eas); Associated with multiple epiphyseal dysplasia type 1.

What condition is associated with COMP p.Pro156= (c.468G>T)?

COMP p.Pro156= (c.468G>T) is associated with multiple epiphyseal dysplasia type 1, pseudoachondroplasia (ClinVar).

How common is COMP p.Pro156= (c.468G>T) in the general population?

COMP p.Pro156= (c.468G>T) is rare (popmax 0.488%, eas) (gnomAD).

How is Multiple epiphyseal dysplasia type 1 inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

COMP p.Pro156=

c.468G>T · rs202241721 · VCV328622

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

rare (popmax 0.488%, eas)

Conditions

multiple epiphyseal dysplasia type 1

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 -12	GERP -4
Overall
CADD	1.688	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.488% East Asian · 215/44,016 alleles

Filtering AF 0.435% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.414%

Overall 0.0224% 345/1,537,218 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.488%	205
Remaining individualsnot grpmax-eligible	0.207%	484
Admixed American	0.00896%	11,161
African / African-American	0.00278%	35,949
European (non-Finnish)	0.000174%	575,126

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: COMP
Protein: p.Pro156=
Coding: c.468G>T
MANE Select: NM_000095
dbSNP: rs202241721
Type: single nucleotide variant
Location: chr19:18789220 (GRCh38)
Gene constraint: LOEUF 1.073 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 88.60 · 1 PDB
Residue 156: the egf-like 2; calcium-binding domain; a disulfide bond

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

Disease context

multiple epiphyseal dysplasia type 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: pseudoachondroplasia

For Multiple epiphyseal dysplasia type 1 (Orphanet):

Inheritance: Autosomal dominant
Onset: Childhood

Similar variants

COMP p.Arg718Trp Pathogenic/Likely pathogenic ★★ ⚠ same condition
COMP p.Asn489Lys Pathogenic/Likely pathogenic ★★ same condition
COMP p.Asn523Lys Pathogenic/Likely pathogenic ★★ same condition
COMP p.Asn555Lys Pathogenic/Likely pathogenic ★★ same condition
COMP p.Asp269Gly Pathogenic/Likely pathogenic ★★ same condition
COMP p.Asp273Val Likely pathogenic ★★ same condition
COMP p.Asp326Asn Pathogenic/Likely pathogenic ★★ same condition
COMP p.Asp349His Pathogenic ★★ 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/comp-p-pro156 (accessed [today's date]).

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