Is ECT2L p.Leu292Phe (c.876A>C) pathogenic?

ECT2L p.Leu292Phe (c.876A>C) is classified Uncertain significance in ECT2L (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-20). AlphaMissense: likely benign (0.2635); Rare (popmax 0.111%, afr).

How common is ECT2L p.Leu292Phe (c.876A>C) in the general population?

ECT2L p.Leu292Phe (c.876A>C) is rare (popmax 0.111%, afr) (gnomAD).

What do computational predictors say about ECT2L p.Leu292Phe (c.876A>C)?

AlphaMissense predicts likely benign (score 0.2635) — an in-silico prediction, not a clinical call.

ECT2L p.Leu292Phe

c.876A>C · rs73557265 · VCV2348343

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2635 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.111%, afr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.2635	likely benign
REVEL	0.424	indeterminate
SaProt	LLR -10.28	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.64	GERP -2.8, phastCons 0.95
Regional constraint	o/e 0.95	unconstrained · MANE · 89 kb · p 0.11 · regional, not allelic
Overall
CADD	19.16	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 0.111% African / African-American · 83/74,610 alleles

Filtering AF 0.0919% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0848%

Overall 0.00666% 107/1,607,074 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.111%	899
Admixed American	0.017%	5,868
Remaining individualsnot grpmax-eligible	0.00804%	12,438
European (non-Finnish)	0.000765%	130,804

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.Leu292Phe
Coding: c.876A>C
MANE Select: NM_001077706
dbSNP: rs73557265
Type: single nucleotide variant
Location: chr6:138846650 (GRCh38)
Gene constraint: LOEUF 1.127 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.75 · 1 PDB

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-leu292phe (accessed [today's date]).

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