Is COMP p.Asn132Lys (c.396C>G) pathogenic?

COMP p.Asn132Lys (c.396C>G) is classified Conflicting classifications of pathogenicity in COMP (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-04-18). AlphaMissense: likely benign (0.1481); Rare (popmax 0.158%, afr); Associated with Inborn genetic diseases.

What condition is associated with COMP p.Asn132Lys (c.396C>G)?

COMP p.Asn132Lys (c.396C>G) is associated with Inborn genetic diseases (ClinVar).

How common is COMP p.Asn132Lys (c.396C>G) in the general population?

COMP p.Asn132Lys (c.396C>G) is rare (popmax 0.158%, afr) (gnomAD).

What do computational predictors say about COMP p.Asn132Lys (c.396C>G)?

AlphaMissense predicts likely benign (score 0.1481) — an in-silico prediction, not a clinical call.

COMP p.Asn132Lys

c.396C>G · rs200638121 · VCV1055714

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1481 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.158%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1481	likely benign
REVEL	0.049	moderately benign-leaning
SaProt	LLR -6.04	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>A here scores Δ0.20 · evaluated, not missing
Constraint at this position
Conservation	phyloP 1.2	GERP -3.7, phastCons 0.75
Regional constraint	o/e 0.84	unconstrained · MANE · 8,351 bp · p 2.2e-07 · regional, not allelic
Overall
CADD	15.24	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 0.158% African / African-American · 112/70,974 alleles

Filtering AF 0.134% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.125%

Overall 0.00859% 128/1,489,422 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.158%	634
Admixed American	0.0178%	5,618
Remaining individualsnot grpmax-eligible	0.0158%	6,337

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.Asn132Lys
Coding: c.396C>G
MANE Select: NM_000095
dbSNP: rs200638121
Type: single nucleotide variant
Location: chr19:18789292 (GRCh38)
Gene constraint: LOEUF 1.073 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 88.60 · 1 PDB
Residue 132: 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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

COMP p.Arg247Ser Uncertain significance ★★ ⚠ same condition
COMP p.Arg352Trp Uncertain significance ★★ ⚠ same condition
COMP p.Arg379Gln Uncertain significance ★★ ⚠ same condition
COMP p.Arg381Leu Uncertain significance ★★ ⚠ same condition
COMP p.Arg665Trp Uncertain significance ★★ ⚠ same condition
COMP p.Arg689Trp Uncertain significance ★★ ⚠ same condition
COMP p.Arg721His Uncertain significance ★★ ⚠ same condition
COMP p.Asp422Gly 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/comp-p-asn132lys (accessed [today's date]).

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