Is COL17A1 p.Ala489= (c.1467G>A) pathogenic?

COL17A1 p.Ala489= (c.1467G>A) is classified Uncertain significance in COL17A1 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-13). Ultra-rare (popmax 0.0117%, amr); Associated with junctional epidermolysis bullosa, non-Herlitz type.

What condition is associated with COL17A1 p.Ala489= (c.1467G>A)?

COL17A1 p.Ala489= (c.1467G>A) is associated with junctional epidermolysis bullosa, non-Herlitz type (ClinVar).

How common is COL17A1 p.Ala489= (c.1467G>A) in the general population?

COL17A1 p.Ala489= (c.1467G>A) is ultra-rare (popmax 0.0117%, amr) (gnomAD).

COL17A1 p.Ala489=

c.1467G>A · rs749900346 · VCV298732

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0117%, amr)

Conditions

junctional epidermolysis bullosa, non-Herlitz type

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.80	acceptor gain · deltas
Pangolin	Δ0.71	gain · loss 0.02 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP -6	GERP -4.1
Overall
CADD	15.92	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0117% Admixed American · 7/60,014 alleles

Filtering AF 0.00543% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0038%

Overall 0.0018% 29/1,614,092 alleles · ultra-rare exomes 26/1,461,872 · genomes 3/152,220 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0117%	8,573
Remaining individualsnot grpmax-eligible	0.008%	12,498
East Asian	0.00668%	14,963
African / African-American	0.00133%	74,946
European (non-Finnish)	0.0011%	90,771

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: COL17A1
Protein: p.Ala489=
Coding: c.1467G>A
MANE Select: NM_000494
dbSNP: rs749900346
Type: single nucleotide variant
Location: chr10:104056002 (GRCh38)
Gene constraint: LOEUF 0.909 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 47.55 · 1 PDB
Residue 489: the 'nonhelical region (nc16)' region

Full COL17A1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

junctional epidermolysis bullosa, non-Herlitz type — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

COL17A1 p.Arg169Ter Pathogenic ★★ same condition
COL17A1 p.Arg72Ter Pathogenic/Likely pathogenic ★★ same condition
COL17A1 p.Arg9Ter Pathogenic ★★ same condition
COL17A1 p.Gly803Ter Pathogenic ★★ same condition
COL17A1 c.3277+3G>C Uncertain significance ★★ same condition
COL17A1 c.*115A>G Uncertain significance ★★ same condition
COL17A1 p.Ala253Val Uncertain significance ★★ ⚠ same condition
COL17A1 p.Ala452Val 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/col17a1-p-ala489 (accessed [today's date]).

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