Is ECEL1 p.Arg110Gly (c.328C>G) pathogenic?

ECEL1 p.Arg110Gly (c.328C>G) is classified Conflicting classifications of pathogenicity in ECEL1 (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2024-11-25). AlphaMissense: likely benign (0.088); Low-frequency (popmax 1.1%, afr); Associated with Inborn genetic diseases.

What condition is associated with ECEL1 p.Arg110Gly (c.328C>G)?

ECEL1 p.Arg110Gly (c.328C>G) is associated with Inborn genetic diseases (ClinVar).

How common is ECEL1 p.Arg110Gly (c.328C>G) in the general population?

ECEL1 p.Arg110Gly (c.328C>G) is low-frequency (popmax 1.1%, afr) (gnomAD).

What do computational predictors say about ECEL1 p.Arg110Gly (c.328C>G)?

AlphaMissense predicts likely benign (score 0.088) — an in-silico prediction, not a clinical call.

ECEL1 p.Arg110Gly

c.328C>G · rs202167077 · VCV709369

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.088 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.1%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.088	likely benign
REVEL	0.443	indeterminate
SaProt	LLR -5.44	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 8.2	GERP 1.2, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 6,497 bp · p 0.15 · regional, not allelic
Overall
CADD	22.3	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 1.1% African / African-American · 803/72,896 alleles

Filtering AF 1.04% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.01%

Overall 0.057% 895/1,571,230 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.1%	91
Remaining individualsnot grpmax-eligible	0.0754%	1,327
Admixed American	0.0587%	1,703
Middle Eastern	0.0457%	2,186
South Asian	0.00344%	29,083
East Asian	0.00234%	42,710
European (non-Finnish)	0.0006%	166,694

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.Arg110Gly
Coding: c.328C>G
MANE Select: NM_004826
dbSNP: rs202167077
Type: single nucleotide variant
Location: chr2:232486326 (GRCh38)
Gene constraint: LOEUF 1.099 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.62
Residue 110: the peptidase m13 domain

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ECEL1 p.Arg756Trp Uncertain significance ★★ ⚠ same condition
ECEL1 p.Gly209Val Uncertain significance ★★ ⚠ same condition
ECEL1 p.Pro34Ser Uncertain significance ★★ ⚠ same condition
ECEL1 p.Ser44Arg Uncertain significance ★★ ⚠ same condition
ECEL1 p.Arg355Gln Likely benign ★★ same condition
ECEL1 c.1990-6C>T Conflicting classifications of pathogenicity ★ same condition
ECEL1 p.Ala109Val Uncertain significance ★ ⚠ same condition
ECEL1 p.Ala175Thr 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/ecel1-p-arg110gly (accessed [today's date]).

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