Is ECEL1 p.Ala42Val (c.125C>T) pathogenic?

ECEL1 p.Ala42Val (c.125C>T) is classified Uncertain significance in ECEL1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-20). AlphaMissense: likely benign (0.1055); Very rare (popmax 0.00813%, amr); Associated with Inborn genetic diseases.

What condition is associated with ECEL1 p.Ala42Val (c.125C>T)?

ECEL1 p.Ala42Val (c.125C>T) is associated with Inborn genetic diseases (ClinVar).

How common is ECEL1 p.Ala42Val (c.125C>T) in the general population?

ECEL1 p.Ala42Val (c.125C>T) is very rare (popmax 0.00813%, amr) (gnomAD).

What do computational predictors say about ECEL1 p.Ala42Val (c.125C>T)?

AlphaMissense predicts likely benign (score 0.1055) — an in-silico prediction, not a clinical call.

ECEL1 p.Ala42Val

c.125C>T · VCV4618218

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1055 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00813%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1055	likely benign
REVEL	0.125	moderately benign-leaning
SaProt	LLR -7.54	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.6	GERP -1.6, phastCons 0.96
Regional constraint	o/e 0.96	unconstrained · MANE · 6,497 bp · p 0.15 · regional, not allelic
Overall
CADD	7.108	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00813% Admixed American · 2/24,592 alleles

Filtering AF 0.00145% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000675%

Overall 0.00127% 17/1,341,782 alleles · very rare exomes 16/1,190,208 · genomes 1/151,574 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00813%	12,296
European (non-Finnish)	0.00142%	70,497

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.Ala42Val
Coding: c.125C>T
MANE Select: NM_004826
Type: single nucleotide variant
Location: chr2:232486529 (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

Disease context

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

Similar variants

ECEL1 p.Ala42Glu 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 p.Arg355Gln Likely benign ★★ same condition
ECEL1 c.1990-6C>T Conflicting classifications of pathogenicity ★ same condition
ECEL1 p.Ala109Val 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-ala42val (accessed [today's date]).

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