Is COMP p.Asp511Val (c.1532A>T) pathogenic?

COMP p.Asp511Val (c.1532A>T) is classified Uncertain significance in COMP (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-13). AlphaMissense: likely pathogenic (0.9924); Absent from gnomAD v4.1.

How common is COMP p.Asp511Val (c.1532A>T) in the general population?

COMP p.Asp511Val (c.1532A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about COMP p.Asp511Val (c.1532A>T)?

AlphaMissense predicts likely pathogenic (score 0.9924) — an in-silico prediction, not a clinical call.

COMP p.Asp511Val

c.1532A>T · rs2055161863 · VCV1038023

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9924 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9924	likely pathogenic · top 7% in COMP
REVEL	0.951	strongly pathogenic-leaning
SaProt	LLR -16.63	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>C here scores Δ0.30 · evaluated, not missing
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	33.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: COMP
Protein: p.Asp511Val
Coding: c.1532A>T
MANE Select: NM_000095
dbSNP: rs2055161863
Type: single nucleotide variant
Location: chr19:18785809 (GRCh38)
Gene constraint: LOEUF 1.073 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 88.60 · 1 PDB
Residue 511: a UniProt-annotated variant site (in psach); a β-strand

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

Similar variants

COMP p.Asp511Glu Pathogenic/Likely pathogenic ★★ same residue
COMP p.Arg718Trp Pathogenic/Likely pathogenic ★★ ⚠ same type
COMP p.Asn489Lys Pathogenic/Likely pathogenic ★★ same type
COMP p.Asn523Lys Pathogenic/Likely pathogenic ★★ same type
COMP p.Asn555Lys Pathogenic/Likely pathogenic ★★ same type
COMP p.Asp269Gly Pathogenic/Likely pathogenic ★★ same type
COMP p.Asp273Val Likely pathogenic ★★ same type
COMP p.Asp326Asn Pathogenic/Likely pathogenic ★★ same type

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-asp511val (accessed [today's date]).

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