Is COMP c.762+12C>A pathogenic?

COMP c.762+12C>A is classified Benign/Likely benign in COMP (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-05-12). Low-frequency (popmax 1.49%, afr); Associated with pseudoachondroplasia.

What condition is associated with COMP c.762+12C>A?

COMP c.762+12C>A is associated with pseudoachondroplasia, multiple epiphyseal dysplasia type 1 (ClinVar).

How common is COMP c.762+12C>A in the general population?

COMP c.762+12C>A is low-frequency (popmax 1.49%, afr) (gnomAD).

How is Pseudoachondroplasia inherited?

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

COMP c.762+12C>A

rs199733531 · VCV255125

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.49%, afr)

Conditions

pseudoachondroplasia

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
Splice region	donor +12	near-intronic (+12 nt from the splice site)
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.92	GERP -3
Non-coding constraint	Z 4.74	1 kb window · o/e 0.66 · regional · uncalibrated
Overall
CADD	4.259	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.49% African / African-American · 1,093/73,354 alleles

Filtering AF 1.42% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.39%

Overall 0.0845% 1,316/1,556,756 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.49%	67
Middle Eastern	0.15%	666
Admixed American	0.137%	730
Remaining individualsnot grpmax-eligible	0.106%	942
European (non-Finnish)	0.00652%	15,347
East Asian	0.00485%	20,613
South Asian	0.00236%	42,422

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
Coding: c.762+12C>A
MANE Select: NM_000095
dbSNP: rs199733531
Type: single nucleotide variant
Location: chr19:18788580 (GRCh38)
Gene constraint: LOEUF 1.073 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 88.60 · 1 PDB

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

Disease context

pseudoachondroplasia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: multiple epiphyseal dysplasia type 1

For Pseudoachondroplasia (Orphanet):

Inheritance: Autosomal dominant
Onset: Infancy, Neonatal
Prevalence: 1-9 / 100 000 (Worldwide)

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-c-762-plus-12c-a (accessed [today's date]).

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