Is COMP p.Asp439Ala (c.1316A>C) pathogenic?

COMP p.Asp439Ala (c.1316A>C) is classified Uncertain significance in COMP (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-15). AlphaMissense: likely pathogenic (0.9944); Absent from gnomAD v4.1.

How common is COMP p.Asp439Ala (c.1316A>C) in the general population?

COMP p.Asp439Ala (c.1316A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about COMP p.Asp439Ala (c.1316A>C)?

AlphaMissense predicts likely pathogenic (score 0.9944) — an in-silico prediction, not a clinical call.

COMP p.Asp439Ala

c.1316A>C · VCV3719608

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9944 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9944	likely pathogenic · top 5% in COMP
REVEL	0.866	moderately pathogenic-leaning
SaProt	LLR -11.33	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	27.6	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.Asp439Ala
Coding: c.1316A>C
MANE Select: NM_000095
Type: single nucleotide variant
Location: chr19:18786138 (GRCh38)
Gene constraint: LOEUF 1.073 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 88.60 · 1 PDB
Residue 439: the 'disordered' region

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

Similar variants

COMP p.Asp439Glu Pathogenic/Likely pathogenic ★★ ⚠ same residue
COMP p.Asp439Gly Likely pathogenic ★★ same residue
COMP p.Asp439Tyr Pathogenic/Likely pathogenic ★★ same residue
COMP p.Asp439Asn Likely pathogenic ★ same residue
COMP p.Asp439= Likely benign ★ 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

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-asp439ala (accessed [today's date]).

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