Is ECT2L p.Val570Ala (c.1709T>C) pathogenic?

ECT2L p.Val570Ala (c.1709T>C) is classified Likely benign in ECT2L (ClinVar, Single submitter, 2 submitters; last evaluated 2022-12-01). AlphaMissense: likely benign (0.1382); Rare (popmax 0.866%, nfe).

How common is ECT2L p.Val570Ala (c.1709T>C) in the general population?

ECT2L p.Val570Ala (c.1709T>C) is rare (popmax 0.866%, nfe) (gnomAD).

What do computational predictors say about ECT2L p.Val570Ala (c.1709T>C)?

AlphaMissense predicts likely benign (score 0.1382) — an in-silico prediction, not a clinical call.

ECT2L p.Val570Ala

c.1709T>C · rs138935097 · VCV133996

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1382 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.866%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1382	likely benign
REVEL	0.159	moderately benign-leaning
SaProt	LLR -4.62	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 1.8	GERP -1.5, phastCons 0.99
Regional constraint	o/e 0.95	unconstrained · MANE · 89 kb · p 0.11 · regional, not allelic
Overall
CADD	15.12	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 0.866% European (non-Finnish) · 10,224/1,179,942 alleles

Filtering AF 0.852% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.847%

Overall 0.696% 11,241/1,613,934 alleles · rare

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	2.97%	34
European (non-Finnish)grpmax	0.866%	115
Remaining individualsnot grpmax-eligible	0.597%	168
Admixed American	0.445%	225
South Asian	0.194%	514
African / African-American	0.149%	670
Finnishnot grpmax-eligible	0.0828%	1,208
Middle Eastern	0.066%	1,516
Ashkenazi Jewishnot grpmax-eligible	0.0135%	7,401

Amish 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: ECT2L
Protein: p.Val570Ala
Coding: c.1709T>C
MANE Select: NM_001077706
dbSNP: rs138935097
Type: single nucleotide variant
Location: chr6:138881000 (GRCh38)
Gene constraint: LOEUF 1.127 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.75 · 1 PDB
Residue 570: the dh domain

Full ECT2L gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ECT2L p.Ala147Thr Uncertain significance ★ ⚠ same type
ECT2L p.Ala161Thr Uncertain significance ★ ⚠ same type
ECT2L p.Ala299Val Uncertain significance ★ ⚠ same type
ECT2L p.Ala401Ser Uncertain significance ★ ⚠ same type
ECT2L p.Ala443Ser Uncertain significance ★ ⚠ same type
ECT2L p.Ala515Gly Uncertain significance ★ ⚠ same type
ECT2L p.Ala599Thr Uncertain significance ★ ⚠ same type
ECT2L p.Ala605Gly Uncertain significance ★ ⚠ 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/ect2l-p-val570ala (accessed [today's date]).

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