Is ECEL1 p.Arg355Gln (c.1064G>A) pathogenic?

ECEL1 p.Arg355Gln (c.1064G>A) is classified Likely benign in ECEL1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-01-26). AlphaMissense: likely benign (0.0707); Ultra-rare (popmax 0.0533%, afr); Associated with Inborn genetic diseases.

What condition is associated with ECEL1 p.Arg355Gln (c.1064G>A)?

ECEL1 p.Arg355Gln (c.1064G>A) is associated with Inborn genetic diseases (ClinVar).

How common is ECEL1 p.Arg355Gln (c.1064G>A) in the general population?

ECEL1 p.Arg355Gln (c.1064G>A) is ultra-rare (popmax 0.0533%, afr) (gnomAD).

What do computational predictors say about ECEL1 p.Arg355Gln (c.1064G>A)?

AlphaMissense predicts likely benign (score 0.0707) — an in-silico prediction, not a clinical call.

ECEL1 p.Arg355Gln

c.1064G>A · rs372254060 · VCV1151649

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0707 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0533%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0707	likely benign
REVEL	0.219	benign-leaning
SaProt	LLR -5.87	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.23	acceptor gain · deltas
Constraint at this position
Conservation	phyloP -0.85	GERP -3.2, phastCons 0.003
Regional constraint	o/e 0.96	unconstrained · MANE · 6,497 bp · p 0.15 · regional, not allelic
Overall
CADD	17.74	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 0.0533% African / African-American · 40/75,046 alleles

Filtering AF 0.0401% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0356%

Overall 0.00843% 136/1,613,908 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0533%	1,876
European (non-Finnish)	0.00746%	13,409
East Asian	0.00446%	22,440
Remaining individualsnot grpmax-eligible	0.0032%	31,252
Finnishnot grpmax-eligible	0.00313%	31,904
Admixed American	0.00167%	60,016
South Asian	0.0011%	91,082

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.Arg355Gln
Coding: c.1064G>A
MANE Select: NM_004826
dbSNP: rs372254060
Type: single nucleotide variant
Location: chr2:232484592 (GRCh38)
Gene constraint: LOEUF 1.099 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.62
Residue 355: a disulfide bond; 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.Arg355Trp Uncertain significance ★ ⚠ same residue
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 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-arg355gln (accessed [today's date]).

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