Is ECEL1 p.Ser240Arg (c.720C>A) pathogenic?

ECEL1 p.Ser240Arg (c.720C>A) is classified Benign in ECEL1 (ClinVar, Single submitter, 2 submitters; last evaluated 2019-12-31). AlphaMissense: likely pathogenic (0.9414); Rare (popmax 0.132%, nfe).

How common is ECEL1 p.Ser240Arg (c.720C>A) in the general population?

ECEL1 p.Ser240Arg (c.720C>A) is rare (popmax 0.132%, nfe) (gnomAD).

What do computational predictors say about ECEL1 p.Ser240Arg (c.720C>A)?

AlphaMissense predicts likely pathogenic (score 0.9414) — an in-silico prediction, not a clinical call.

ECEL1 p.Ser240Arg

c.720C>A · rs191821453 · VCV731475

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9414 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.132%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9414	likely pathogenic
REVEL	0.543	indeterminate
SaProt	LLR -3.17	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.3	GERP -2.3, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 6,497 bp · p 0.15 · regional, not allelic
Overall
CADD	24.4	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 0.132% European (non-Finnish) · 1,540/1,164,928 alleles

Filtering AF 0.127% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.124%

Overall 0.158% 2,501/1,578,876 alleles · rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	1.56%	64
European (non-Finnish)grpmax	0.132%	756
Remaining individualsnot grpmax-eligible	0.0817%	1,224
African / African-American	0.0202%	4,957
Admixed American	0.00902%	11,087

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.Ser240Arg
Coding: c.720C>A
MANE Select: NM_004826
dbSNP: rs191821453
Type: single nucleotide variant
Location: chr2:232485934 (GRCh38)
Gene constraint: LOEUF 1.099 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.62
Residue 240: a disulfide bond; the peptidase m13 domain

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-ser240arg (accessed [today's date]).

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