Is ECEL1 p.Arg390His (c.1169G>A) pathogenic?

ECEL1 p.Arg390His (c.1169G>A) is classified Likely benign in ECEL1 (ClinVar, Single submitter, 2 submitters; last evaluated 2022-04-02). AlphaMissense: likely benign (0.071); Rare (popmax 0.188%, afr).

How common is ECEL1 p.Arg390His (c.1169G>A) in the general population?

ECEL1 p.Arg390His (c.1169G>A) is rare (popmax 0.188%, afr) (gnomAD).

What do computational predictors say about ECEL1 p.Arg390His (c.1169G>A)?

AlphaMissense predicts likely benign (score 0.071) — an in-silico prediction, not a clinical call.

ECEL1 p.Arg390His

c.1169G>A · rs149225442 · VCV1150732

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.071 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.188%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.071	likely benign
REVEL	0.201	benign-leaning
SaProt	LLR -6.17	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.37 · evaluated, not missing
Constraint at this position
Conservation	phyloP -1.5	GERP -0.76
Regional constraint	o/e 0.96	unconstrained · MANE · 6,497 bp · p 0.15 · regional, not allelic
Overall
CADD	22.2	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 0.188% African / African-American · 141/75,056 alleles

Filtering AF 0.163% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.153%

Overall 0.0101% 163/1,613,854 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.188%	532
Middle Eastern	0.0165%	6,060
Remaining individualsnot grpmax-eligible	0.008%	12,501
Admixed American	0.00333%	30,014
East Asian	0.00223%	44,878
European (non-Finnish)	0.0011%	90,768

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.Arg390His
Coding: c.1169G>A
MANE Select: NM_004826
dbSNP: rs149225442
Type: single nucleotide variant
Location: chr2:232484487 (GRCh38)
Gene constraint: LOEUF 1.099 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.62
Residue 390: a disulfide bond; the peptidase m13 domain

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

Similar variants

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ECEL1 c.2151+2T>C Likely pathogenic ★★ same type
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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-arg390his (accessed [today's date]).

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