Is ECM2 p.Leu633Arg (c.1898T>G) pathogenic?

ECM2 p.Leu633Arg (c.1898T>G) is classified Uncertain significance in ECM2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-08). AlphaMissense: likely pathogenic (0.9662); Absent from gnomAD v4.1.

How common is ECM2 p.Leu633Arg (c.1898T>G) in the general population?

ECM2 p.Leu633Arg (c.1898T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ECM2 p.Leu633Arg (c.1898T>G)?

AlphaMissense predicts likely pathogenic (score 0.9662) — an in-silico prediction, not a clinical call.

ECM2 p.Leu633Arg

c.1898T>G · rs2492020126 · VCV2305605

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9662 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9662	likely pathogenic
REVEL	0.958	strongly pathogenic-leaning
SaProt	LLR -15.28	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 11	GERP 2.5, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 27 kb · p 0.0043 · regional, not allelic
Overall
CADD	28.7	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ECM2
Protein: p.Leu633Arg
Coding: c.1898T>G
MANE Select: NM_001012267 · reported on NM_001393
dbSNP: rs2492020126
Type: single nucleotide variant
Location: chr9:92500760 (GRCh38)

Full ECM2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

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/ecm2-p-leu633arg (accessed [today's date]).

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