Is ECEL1 p.Leu52Pro (c.155T>C) pathogenic?

ECEL1 p.Leu52Pro (c.155T>C) is classified Likely benign in ECEL1 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-12-01). AlphaMissense: likely benign (0.0723); Rare (popmax 0.695%, nfe).

How common is ECEL1 p.Leu52Pro (c.155T>C) in the general population?

ECEL1 p.Leu52Pro (c.155T>C) is rare (popmax 0.695%, nfe) (gnomAD).

What do computational predictors say about ECEL1 p.Leu52Pro (c.155T>C)?

AlphaMissense predicts likely benign (score 0.0723) — an in-silico prediction, not a clinical call.

ECEL1 p.Leu52Pro

c.155T>C · rs564717204 · VCV707886

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.0723 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.695%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.0723	likely benign
REVEL	0.527	indeterminate
SaProt	LLR -5.55	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.6	GERP 0.94, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 6,497 bp · p 0.15 · regional, not allelic
Overall
CADD	20.8	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 0.695% European (non-Finnish) · 7,491/1,078,528 alleles

Filtering AF 0.681% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.676%

Overall 0.605% 8,367/1,382,718 alleles · rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.796%	126
European (non-Finnish)grpmax	0.695%	144
Remaining individualsnot grpmax-eligible	0.504%	199
South Asian	0.265%	377
Admixed American	0.239%	418
Middle Eastern	0.104%	959
African / African-American	0.0949%	1,054
Ashkenazi Jewishnot grpmax-eligible	0.0136%	7,339

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.Leu52Pro
Coding: c.155T>C
MANE Select: NM_004826
dbSNP: rs564717204
Type: single nucleotide variant
Location: chr2:232486499 (GRCh38)
Gene constraint: LOEUF 1.099 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.62

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

Similar variants

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
ECEL1 p.Gln435Ter Pathogenic/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-leu52pro (accessed [today's date]).

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