Is COMP p.Asp317Glu (c.951C>A) pathogenic?

COMP p.Asp317Glu (c.951C>A) is classified Likely benign in COMP (ClinVar, Single submitter, 3 submitters; last evaluated 2025-07-28). AlphaMissense: likely pathogenic (0.9734); Ultra-rare (popmax 0.0217%, nfe).

How common is COMP p.Asp317Glu (c.951C>A) in the general population?

COMP p.Asp317Glu (c.951C>A) is ultra-rare (popmax 0.0217%, nfe) (gnomAD).

What do computational predictors say about COMP p.Asp317Glu (c.951C>A)?

AlphaMissense predicts likely pathogenic (score 0.9734) — an in-silico prediction, not a clinical call.

COMP p.Asp317Glu

c.951C>A · rs200547692 · VCV1205927

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.9734 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0217%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9734	likely pathogenic
REVEL	0.696	pathogenic-leaning
SaProt	LLR -13.98	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 -0.7	GERP -4
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 0.0217% European (non-Finnish) · 256/1,179,978 alleles

Filtering AF 0.0195% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0186%

Overall 0.0181% 292/1,613,050 alleles · ultra-rare exomes 270/1,460,900 · genomes 22/152,150 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0272%	3,675
Finnishnot grpmax-eligible	0.0269%	3,713
European (non-Finnish)grpmax	0.0217%	4,609
African / African-American	0.00267%	37,457

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Asp317Glu
Coding: c.951C>A
MANE Select: NM_000095
dbSNP: rs200547692
Type: single nucleotide variant
Location: chr19:18788236 (GRCh38)
Gene constraint: LOEUF 1.073 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 88.60 · 1 PDB
Residue 317: a turn; the 'disordered' region; a UniProt-annotated variant site (in edm1; atypical form)

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

Similar variants

COMP p.Asp317Asn Pathogenic ★ same residue
COMP p.Asp317Tyr Likely pathogenic ★ same residue
COMP p.Asp317Gly Conflicting classifications of pathogenicity ★ ⚠ same residue
COMP p.Asp317Val Conflicting classifications of pathogenicity ★ ⚠ 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

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-asp317glu (accessed [today's date]).

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