Is COL17A1 p.Pro736= (c.2208C>T) pathogenic?

COL17A1 p.Pro736= (c.2208C>T) is classified Benign in COL17A1 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-01-28). Low-frequency (popmax 3.28%, sas); Associated with junctional epidermolysis bullosa, non-Herlitz type.

What condition is associated with COL17A1 p.Pro736= (c.2208C>T)?

COL17A1 p.Pro736= (c.2208C>T) is associated with junctional epidermolysis bullosa, non-Herlitz type (ClinVar).

How common is COL17A1 p.Pro736= (c.2208C>T) in the general population?

COL17A1 p.Pro736= (c.2208C>T) is low-frequency (popmax 3.28%, sas) (gnomAD).

COL17A1 p.Pro736=

c.2208C>T · rs139559170 · VCV298717

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

low-frequency (popmax 3.28%, sas)

Conditions

junctional epidermolysis bullosa, non-Herlitz type

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -8.2	GERP -4.3
Overall
CADD	7.044	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 3.28% South Asian · 2,986/91,072 alleles

Filtering AF 3.18% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.14%

Overall 0.222% 3,577/1,614,166 alleles · low-frequency exomes 3,382/1,461,874 · genomes 195/152,292 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	3.28%	30
Middle Eastern	0.264%	379
Remaining individualsnot grpmax-eligible	0.245%	409
Ashkenazi Jewishnot grpmax-eligible	0.0473%	2,115
European (non-Finnish)	0.0324%	3,089
Admixed American	0.0267%	3,752
African / African-American	0.0107%	9,381
East Asian	0.00223%	44,890
Finnishnot grpmax-eligible	0.00156%	64,036

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.Pro736=
Coding: c.2208C>T
MANE Select: NM_000494
dbSNP: rs139559170
Type: single nucleotide variant
Location: chr10:104049428 (GRCh38)
Gene constraint: LOEUF 0.909 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 47.55 · 1 PDB
Residue 736: the 'disordered' region; the 'triple-helical region' region; an α-helix

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-pro736 (accessed [today's date]).

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