Is KEL p.Pro560= (c.1680A>C) pathogenic?

KEL p.Pro560= (c.1680A>C) is classified Benign in KEL (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-11-25). Common (popmax 18.9%, afr) — too common for a highly-penetrant pathogenic allele; Associated with KEL-related disorder.

What condition is associated with KEL p.Pro560= (c.1680A>C)?

KEL p.Pro560= (c.1680A>C) is associated with KEL-related disorder (ClinVar).

KEL p.Pro560=

Q: How common is KEL p.Pro560= (c.1680A>C) in the general population?

KEL p.Pro560= (c.1680A>C) is common (popmax 18.9%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1680A>C · rs8176036 · VCV3038127

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Common

common (popmax 18.9%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

KEL-related disorder

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 -14	GERP -11
Overall
CADD	0.033	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 18.9% African / African-American · 14,202/74,968 alleles

Filtering AF 18.7% ClinGen BA1/BS1 input FAF95, joint · FAF99 18.6%

Overall 5.51% 88,943/1,613,774 alleles · common exomes 75,536/1,461,586 · genomes 13,407/152,188 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	18.9%	5
Finnishnot grpmax-eligible	7.27%	14
Remaining individualsnot grpmax-eligible	5.56%	18
European (non-Finnish)	5.26%	19
Admixed American	3.33%	30
Ashkenazi Jewishnot grpmax-eligible	2.95%	34
Middle Eastern	2.56%	39
East Asian	1.95%	51
South Asian	0.741%	135
Amishnot grpmax-eligible	0.658%	152

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: KEL
Protein: p.Pro560=
Coding: c.1680A>C
MANE Select: NM_000420
dbSNP: rs8176036
Type: single nucleotide variant
Location: chr7:142943509 (GRCh38)
Gene constraint: LOEUF 1.11 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.46
Residue 560: the peptidase m13 domain

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

Disease context

KEL-related disorder

Similar variants

KEL p.Ala311Asp Uncertain significance ★ ⚠ same condition
KEL c.223+1G>C Pathogenic same condition
KEL c.1593-4A>T Benign same condition
KEL c.1703+5G>A Likely benign same condition
KEL c.736-10C>T Likely benign same condition
KEL p.Glu494Val Likely benign same condition
KEL p.Leu633= Benign same condition
KEL p.Thr421= Likely benign 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/kel-p-pro560 (accessed [today's date]).

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