Is COMP p.Ala624Val (c.1871C>T) pathogenic?

COMP p.Ala624Val (c.1871C>T) is classified Uncertain significance in COMP (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-16). AlphaMissense: ambiguous (0.5327); Very rare (popmax 0.00383%, amr).

How common is COMP p.Ala624Val (c.1871C>T) in the general population?

COMP p.Ala624Val (c.1871C>T) is very rare (popmax 0.00383%, amr) (gnomAD).

What do computational predictors say about COMP p.Ala624Val (c.1871C>T)?

AlphaMissense predicts ambiguous (score 0.5327) — an in-silico prediction, not a clinical call.

COMP p.Ala624Val

c.1871C>T · rs201624503 · VCV1429802

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.5327 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00383%, amr)

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.5327	ambiguous
REVEL	0.709	pathogenic-leaning
SaProt	LLR -10.14	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense makes no call.
Splicing
SpliceAI	Δ0.98	donor gain · deltas
Pangolin	Δ0.61	gain · loss 0.35 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 12	GERP 2, phastCons 1
Regional constraint	o/e 0.84	unconstrained · MANE · 8,351 bp · p 2.2e-07 · regional, not allelic
Overall
CADD	36.0	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 0.00383% Admixed American · 2/52,282 alleles

Filtering AF 0.000634% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000237%

Overall 0.000767% 12/1,565,300 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00383%	26,141
African / African-American	0.00273%	36,642
Remaining individualsnot grpmax-eligible	0.00164%	60,930
South Asian	0.00117%	85,616
European (non-Finnish)	0.000517%	193,398

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.Ala624Val
Coding: c.1871C>T
MANE Select: NM_000095
dbSNP: rs201624503
Type: single nucleotide variant
Location: chr19:18784939 (GRCh38)
Gene constraint: LOEUF 1.073 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 88.60 · 1 PDB
Residue 624: the tsp c-terminal domain; the 'mediates cell survival and induction of the iap family of survival proteins' region; a disulfide bond

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

Similar variants

COMP p.Ala624= Likely benign ★★ same residue
COMP p.Ala624Thr Uncertain significance ★ ⚠ 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

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-ala624val (accessed [today's date]).

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