Is COL18A1 p.Ala1026Val (c.3077C>T) pathogenic?

COL18A1 p.Ala1026Val (c.3077C>T) is classified Likely benign in COL18A1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-12-05). AlphaMissense: likely benign (0.1007); Rare (popmax 0.134%, eas).

How common is COL18A1 p.Ala1026Val (c.3077C>T) in the general population?

COL18A1 p.Ala1026Val (c.3077C>T) is rare (popmax 0.134%, eas) (gnomAD).

What do computational predictors say about COL18A1 p.Ala1026Val (c.3077C>T)?

AlphaMissense predicts likely benign (score 0.1007) — an in-silico prediction, not a clinical call.

COL18A1 p.Ala1026Val

c.3077C>T · rs557054483 · VCV1084474

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1007 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.134%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1007	likely benign
REVEL	0.115	moderately benign-leaning
SaProt	LLR -7.04	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.8	GERP 1, phastCons 0.32
Regional constraint	o/e 1.10	unconstrained · MANE · 107 kb · p 4.9e-06 · regional, not allelic
Overall
CADD	16.41	PHRED · no single calibrated threshold — expert panels disagree

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM A1441V vs ClinVar A1026V) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.134% East Asian · 59/44,140 alleles

Filtering AF 0.106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0965%

Overall 0.00405% 63/1,555,054 alleles · rare exomes 54/1,402,832 · genomes 9/152,222 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.134%	748
Remaining individualsnot grpmax-eligible	0.00496%	20,150
Admixed American	0.00178%	56,046

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: COL18A1
Protein: p.Ala1026Val
Coding: c.3077C>T
MANE Select: NM_001379500
dbSNP: rs557054483
Type: single nucleotide variant
Location: chr21:45505421 (GRCh38)
Gene constraint: LOEUF 1.001 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 51.77 · 9 PDB
Residue 1441 UniProt numbering: the 'triple-helical region 10 (col10)' region; the 'disordered' region

Full COL18A1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

COL18A1 p.Ala1026Gly Uncertain significance ★ ⚠ same residue
COL18A1 p.Ala1026Thr Conflicting classifications of pathogenicity ★ ⚠ same residue
COL18A1 c.1897-2A>G Likely pathogenic ★★ same type
COL18A1 c.2157+1G>A Likely pathogenic ★★ same type
COL18A1 c.2577+1G>A Pathogenic/Likely pathogenic ★★ same type
COL18A1 c.3013+3A>C Likely pathogenic ★★ same type
COL18A1 c.3809+2T>C Pathogenic ★★ same type
COL18A1 c.798+1G>T 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/col18a1-p-ala1026val (accessed [today's date]).

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