Is COMP p.Asn386Asp (c.1156A>G) pathogenic?

COMP p.Asn386Asp (c.1156A>G) is classified Benign/Likely benign in COMP (ClinVar, Multiple submitters, 8 submitters; last evaluated 2026-05-09). AlphaMissense: likely pathogenic (0.8214); Common (popmax 5.16%, nfe) — too common for a highly-penetrant pathogenic allele; Associated with connective tissue disorder.

What condition is associated with COMP p.Asn386Asp (c.1156A>G)?

COMP p.Asn386Asp (c.1156A>G) is associated with connective tissue disorder, multiple epiphyseal dysplasia type 1, pseudoachondroplasia (ClinVar).

What do computational predictors say about COMP p.Asn386Asp (c.1156A>G)?

AlphaMissense predicts likely pathogenic (score 0.8214) — an in-silico prediction, not a clinical call.

COMP p.Asn386Asp

Q: How common is COMP p.Asn386Asp (c.1156A>G) in the general population?

COMP p.Asn386Asp (c.1156A>G) is common (popmax 5.16%, nfe) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1156A>G · rs61739916 · VCV40987

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

AlphaMissense

likely pathogenic

0.8214 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 5.16%, nfe) — too common for a highly-penetrant pathogenic allele

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

connective tissue disorder

Computational evidence

Protein change
AlphaMissense	0.8214	likely pathogenic
REVEL	0.808	moderately pathogenic-leaning
SaProt	LLR -13.11	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 2, phastCons 1
Regional constraint	o/e 0.84	unconstrained · MANE · 8,351 bp · p 2.2e-07 · regional, not allelic
Overall
CADD	25.7	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 5.16% European (non-Finnish) · 60,838/1,179,654 alleles

Filtering AF 5.12% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.11%

Overall 4.45% 71,729/1,613,698 alleles · common

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	5.16%	19
Remaining individualsnot grpmax-eligible	4.33%	23
South Asian	3.67%	27
Middle Eastern	3.2%	31
Ashkenazi Jewishnot grpmax-eligible	2.98%	34
Finnishnot grpmax-eligible	2.96%	34
Admixed American	2.07%	48
Amishnot grpmax-eligible	1.21%	83
African / African-American	0.824%	121
East Asian	0.00891%	11,220

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.Asn386Asp
Coding: c.1156A>G
MANE Select: NM_000095
dbSNP: rs61739916
Type: single nucleotide variant
Location: chr19:18786630 (GRCh38)
Gene constraint: LOEUF 1.073 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 88.60 · 1 PDB
Residue 386: the 'disordered' region

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

Disease context

connective tissue disorder — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: multiple epiphyseal dysplasia type 1 pseudoachondroplasia

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-asn386asp (accessed [today's date]).

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