Is ECEL1 p.Pro513= (c.1539G>A) pathogenic?

ECEL1 p.Pro513= (c.1539G>A) is classified Likely benign in ECEL1 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-10-12). Ultra-rare (popmax 0.0165%, mid).

How common is ECEL1 p.Pro513= (c.1539G>A) in the general population?

ECEL1 p.Pro513= (c.1539G>A) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

ECEL1 p.Pro513=

c.1539G>A · rs199916648 · VCV792296

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -14	GERP -3.5
Overall
CADD	6.544	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0165% Middle Eastern · 1/6,058 alleles

Filtering AF 0.00435% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00396%

Overall 0.00864% 139/1,608,570 alleles · ultra-rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.098%	1,021
Middle Easterngrpmax	0.0165%	6,058
East Asian	0.00897%	11,151
Remaining individualsnot grpmax-eligible	0.00642%	15,584
European (non-Finnish)	0.00543%	18,407
Ashkenazi Jewishnot grpmax-eligible	0.0034%	29,386
South Asian	0.00222%	45,131
African / African-American	0.00133%	74,992

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: ECEL1
Protein: p.Pro513=
Coding: c.1539G>A
MANE Select: NM_004826
dbSNP: rs199916648
Type: single nucleotide variant
Location: chr2:232483147 (GRCh38)
Gene constraint: LOEUF 1.099 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.62
Residue 513: a disulfide bond; the peptidase m13 domain

Full ECEL1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ECEL1 p.Pro513Leu Uncertain significance ★ ⚠ same residue
ECEL1 c.1685+1G>A Pathogenic ★★ same type
ECEL1 c.2151+2T>C Likely pathogenic ★★ same type
ECEL1 c.966+1G>A Pathogenic ★★ same type
ECEL1 p.Ala675Thr Pathogenic ★★ same type
ECEL1 p.Arg333Ter Pathogenic ★★ same type
ECEL1 p.Arg395Gln Pathogenic/Likely pathogenic ★★ ⚠ same type
ECEL1 p.Arg418Cys 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/ecel1-p-pro513 (accessed [today's date]).

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