Is COL8A2 p.Pro480Leu (c.1439C>T) pathogenic?

COL8A2 p.Pro480Leu (c.1439C>T) is classified Uncertain significance in COL8A2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-28). AlphaMissense: likely benign (0.1253); Very rare (popmax 0.00786%, amr); Associated with Inborn genetic diseases.

What condition is associated with COL8A2 p.Pro480Leu (c.1439C>T)?

COL8A2 p.Pro480Leu (c.1439C>T) is associated with Inborn genetic diseases (ClinVar).

How common is COL8A2 p.Pro480Leu (c.1439C>T) in the general population?

COL8A2 p.Pro480Leu (c.1439C>T) is very rare (popmax 0.00786%, amr) (gnomAD).

What do computational predictors say about COL8A2 p.Pro480Leu (c.1439C>T)?

AlphaMissense predicts likely benign (score 0.1253) — an in-silico prediction, not a clinical call.

COL8A2 p.Pro480Leu

c.1439C>T · VCV3835451

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1253 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00786%, amr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1253	likely benign
REVEL	0.867	moderately pathogenic-leaning
SaProt	LLR -10.29	damaging
⇒ REVEL and SaProt call this damaging; AlphaMissense does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.8	GERP 2.1, phastCons 1
Regional constraint	o/e 0.35	constrained · MANE · 66 bp · p 0.00057 · regional, not allelic
Overall
CADD	24.4	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 0.00786% Admixed American · 4/50,902 alleles

Filtering AF 0.00614% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00566%

Overall 0.00635% 98/1,544,326 alleles · very rare exomes 89/1,392,532 · genomes 9/151,794 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00786%	12,725
European (non-Finnish)	0.00742%	13,471
Remaining individualsnot grpmax-eligible	0.0067%	14,918
African / African-American	0.00549%	18,205
East Asian	0.00245%	40,780

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: COL8A2
Protein: p.Pro480Leu
Coding: c.1439C>T
MANE Select: NM_005202
Type: single nucleotide variant
Location: chr1:36098242 (GRCh38)
Gene constraint: LOEUF 1.139 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 58.03
Residue 480: the 'disordered' region; the 'triple-helical region' region

Full COL8A2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

COL8A2 p.Arg149Gln Uncertain significance ★★ ⚠ same condition
COL8A2 p.Arg263Ser Uncertain significance ★★ ⚠ same condition
COL8A2 p.Arg372Cys Uncertain significance ★★ ⚠ same condition
COL8A2 p.Glu568Lys Uncertain significance ★★ ⚠ same condition
COL8A2 p.Gly549Ser Uncertain significance ★★ ⚠ same condition
COL8A2 p.Gly550Ser Uncertain significance ★★ ⚠ same condition
COL8A2 p.Gly559Glu Uncertain significance ★★ ⚠ same condition
COL8A2 p.Gly601Ala Uncertain significance ★★ ⚠ same condition

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/col8a2-p-pro480leu (accessed [today's date]).

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