Is COMP p.Pro234Ser (c.700C>T) pathogenic?

COMP p.Pro234Ser (c.700C>T) is classified Conflicting classifications of pathogenicity in COMP (ClinVar, Conflicting submitters, 6 submitters; last evaluated 2026-04-27). AlphaMissense: likely benign (0.0767); Rare (popmax 0.105%, mid); Associated with pseudoachondroplasia.

What condition is associated with COMP p.Pro234Ser (c.700C>T)?

COMP p.Pro234Ser (c.700C>T) is associated with pseudoachondroplasia, multiple epiphyseal dysplasia type 1 (ClinVar).

How common is COMP p.Pro234Ser (c.700C>T) in the general population?

COMP p.Pro234Ser (c.700C>T) is rare (popmax 0.105%, mid) (gnomAD).

How is Pseudoachondroplasia inherited?

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

What do computational predictors say about COMP p.Pro234Ser (c.700C>T)?

AlphaMissense predicts likely benign (score 0.0767) — an in-silico prediction, not a clinical call.

COMP p.Pro234Ser

c.700C>T · rs557483957 · VCV890212

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 6 submitters

AlphaMissense

likely benign

0.0767 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.105%, mid)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

pseudoachondroplasia

Computational evidence

Protein change
AlphaMissense	0.0767	likely benign
REVEL	0.423	indeterminate
SaProt	LLR -10.27	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 0.18, phastCons 1
Regional constraint	o/e 0.84	unconstrained · MANE · 8,351 bp · p 2.2e-07 · regional, not allelic
Overall
CADD	22.3	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 0.105% Middle Eastern · 6/5,738 alleles

Filtering AF 0.0455% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0415%

Overall 0.0393% 608/1,545,806 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.105%	956
European (non-Finnish)	0.0461%	2,171
South Asian	0.0429%	2,333
Remaining individualsnot grpmax-eligible	0.035%	2,856
Ashkenazi Jewishnot grpmax-eligible	0.014%	7,151
Admixed American	0.0137%	7,281
African / African-American	0.00684%	14,626
Finnishnot grpmax-eligible	0.00181%	55,190

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.Pro234Ser
Coding: c.700C>T
MANE Select: NM_000095
dbSNP: rs557483957
Type: single nucleotide variant
Location: chr19:18788654 (GRCh38)
Gene constraint: LOEUF 1.073 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 88.60 · 1 PDB
Residue 234: a β-strand; a disulfide bond; the egf-like 4 domain; a UniProt-annotated variant site (in psach)

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-p-pro234ser (accessed [today's date]).

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